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PRL activates STAT5. 466 / 487
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"By blocking these kinases in both OVCAR3 and FT33-Tag-Myc cells, it was identified that PRL treatment mainly activated ERK, STAT5 and m-TOR to stimulate cellular proliferation and transformation in hu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"We have used the prolactin activation of Stat5 and the transcription of a beta -casein promoter luciferase gene reporter construct as a model to study the functional interaction between p53 and the cy[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Prolactin (PRL) and its receptor (PRLR) activate JAK2/STAT5 signaling in BC, which is modulated by inhibitors like suppressors of cytokine signaling (SOCS) proteins and protein inhibitors of activated STAT (PIAS)."

sparser
"Panel B of Fig. 5 shows that induction of ΔS2SF1b had no effect on the activation of Stat5 by PRL."

sparser
"Thus, whether Stat5-related effects are examined at 15 minutes or 24 h, increased expression of ΔS2SF1b had no effect on Stat5 activation by PRL."

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"In epidemiologic studies, the presence of prolactin and phosphorylated signal transducer and activator of transcription 5 (STAT5) in human prostate cancers is linked with high-grade tumors and more aggressive disease [XREF_BIBR]; therefore, targeting autocrine and/or paracrine prolactin mediated activation of STAT5 may represent a novel therapeutic target for patients with prostate cancer."

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"XREF_BIBR, XREF_BIBR Restoring PRL receptor expression in TNBC cell lines decreases their invasive capacity while blocking JAK2 and STAT5 in luminal breast cancer cell lines increases their invasiveness, suggesting that PRL activation of STAT5 restricts the metastatic potential of breast tumors."

trips
"Depletion of PIKE-A in HC11 epithelial cells diminished PRL-induced STAT5 activation and cyclin D1 expression, resulting in profoundly impaired cell proliferation in vitro."

sparser
"Furthermore, it has been described that c-Src is a key node in STAT5 activation by Prl both in normal and malignant breast cells [50] ."

sparser
"Therefore, the similar activation of STAT5, AKT and ERK1/2 by Prl and dexmedetomidine could be explained by Src mediation in every case."

sparser
"STAT5 is activated by prolactin and it controls mammary alveolar development during pregnancy and the activation of genetic programs resulting in lactation xref , xref ."

sparser
"Activation of STAT3 during involution could thus induce SOCS3 expression, which could then prevent STAT5 activation by PRL."

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"While cytokine i.e. GH and PRL induced activation of STAT5 is mediated by the janus kinase (JAK) 2, [3,20-22], in insulin signalling, JAK2 dependent and independent STAT5 activation was reported [3,23[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"It has recently been shown that activation of Stat5 by PRL stimulates 3beta-HSD type 2 transcription and this effect was dependent on the Stat5 binding element [3]."

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"It is well known that PRL and GH are important modulators of lipid metabolism and are also potent inducers of STAT5 in adipocytes [XREF_BIBR, XREF_BIBR]."

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"We have found that in HC11 cells, Stat5 is specifically activated by PRL treatment, demonstrating that Stat5 is a physiological substrate downstream of PRLR."

sparser
"For example, prolactin activates STAT5 to control proliferation, differentiation and survival xref , while STAT3 is activated by IL-6 and LIF to control cell death during involution xref ."

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"This is because mammary-selective promoters such as MMTV or WAP have the progesterone receptor and STAT5-binding sites (Chalepakis et al. 1988; Préfontaine et al. 1999) and are induced during pregnancy and lactation when high progesterone and prolactin levels activate progesterone receptor and STAT5."

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"In Pb-PRL mice, PRLR/STAT5 signaling is triggered in the luminal epithelium by locally produced PRL ( Figure 4 F)."

sparser
"A mouse model of Stat5 activation by Prl recapitulates prostate tumorigenesis from precancerous lesions to invasive carcinoma [75] ."

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"Prolactin activation of Stat5 in human breast cancer cell lines is disrupted by moderate extracellular acidosis."

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"We conclude that prolactin induced Stat5 activation in human breast cancer cell lines is highly sensitive to moderate pH reduction."

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"In contrast, in both cell lines at pH e of 6.8, prolactin activation of Stat5 was greatly suppressed at all prolactin concentrations tested."

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"Stat5 is activated by prolactin, and its presence is mandatory for the proliferation and differentiation of mammary epithelium during pregnancy."

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"At pH e of 7.4 prolactin induced Stat5 activation peaked within 15 min, dropping slightly thereafter in both cell lines, whereas prolactin induced pYStat5 levels were greatly diminished at pH e 6.8, without evidence of emergence of a delayed signal."

sparser
"Prolactin-induced activation of STAT5 within the hypothalamic arcuate nucleus."

sparser
"In T47D, sol IGF-1R inhibited neither GH- nor PRL-induced STAT5 activation."

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"Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects."

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"SKBR3 cells were preincubated alternately at pH e 7.4 or pH e 6.8 for 30 min, before cells were exposed to medium containing prolactin or vehicle for 15 min at either the same pH e or the alternate pH e, and prolactin induced Stat5, Jak2 and Erk signals were examined."

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"In mammary epithelial cells, cortisol binding to the GR in the presence of prolactin activated Stat5 and insulin treatment results in increased beta-casein production independent of a traditional pali[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Some growth factors also appear to be associated with specific STATs, for instance, colony-stimulating factor 1 and EGF stimulate STAT1, STAT3, and STAT5, whereas PDGF stimulates STAT1 and STAT3, and GH and prolactin stimulate only STAT5 [10,27]."

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"This model of paracrine PRL produced in the tumor microenvironment is an interesting area for further investigation in both primary and secondary tumor formation.A wide body of evidence points to a ro[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Rather PRL activation of Stat5, principally Stat5b, occurred in association with luteinization."

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"XREF_BIBR Growth hormones and prolactin are activators of STAT5 and induce lipolysis."

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"As previously mentioned, the expression of the PDK4 gene is mediated by GH- and prolactin stimulated STAT5 activation in adipocytes."

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"Since in previous studies PRL induced STAT5 activation in absence of E 2 and ERalpha was found to interact with STAT5 in Re-ChIP assay [XREF_BIBR], we initially investigated whether STAT5a or STAT5b associated with ERalpha."

sparser
"The prolactin-activated transcription factor STAT5 binds to tandem sites that coincide with activating histone enhancer marks and additional transcription components."

sparser
"However, we have reported that in human breast cancer cell lines Jak1 is also recruited in a Jak2-dependent manner for maximal PRL-activation of Stat5 and other signaling mediators [ xref ]."

sparser
"As an example, interleukin 6 and prolactin activate STAT3 and STAT5, respectively, to enhance the transcription of target genes in their target cell types [ xref , xref ]."

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"T lymphocytes activation mediated by prolactin pathways, prolactin receptors (PRL-R) and JAK2/Stat5, lead to the production and release of a range of cytokines including IL-1, IL-4, IL-5, IL-6, IL-10 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Each of the positive control cytokines induced phospho-JAK2, phospho-STAT3 and/or phospho-STAT5 as reported : IL-6 receptor stimulation activated phospho-JAK2 and phospho-STAT3, PRL receptor stimulati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"We showed previously that PRL, via Jak2, induces binding of Stat5 to a distal GAS site (GAS1) in the cyclin D1 promoter."

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"REGN2878-DM1 also inhibited prolactin-induced STAT5 activity in the HEK293/PRLR/STAT5-Luc reporter cell line, demonstrating inhibition of PRLR signaling."

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"The individual effect of the STAT5 inducer PRL on the number of insulin- and hydrocortisone treated GFP expressing cells was time- and dose dependent, and was more pronounced for the high-GFP expressors than for the total GFP expressing cell population."

sparser
"We have shown that the STAT5-dependent immediate early gene, CIS1 (Cytokine-Inducible SH2 domain-containing protein-1), suppresses PRL-induced STAT5 activation in vitro as well as in transgenic mice."

sparser
"Interestingly, Y532 has been shown to be unnecessary for STAT5 activation, although CIS1 overexpression suppressed PRL-induced STAT5 activation."

sparser
"PRL activates STAT5 when it binds to the prolactin receptor and induces immunoglobulin synthesis and anti-dsDNA in SLE lymphocytes xref – xref ."

sparser
"In addition, Prl-induced Stat5 activation increased Jak2 mRNA levels by 80-120% in PC cells, which was blocked by genetic knockdown of Stat5 by shRNA ( xref , xref )."

sparser
"These include lactogenic hormone response elements, such as GAS motifs bound by the prolactin-activated transcription factor STAT5, glucocorticoid response elements (GREs) and sites recognized by NFIB, another key TF to the 10,000-fold stimulation of casein gene expression during pregnancy and lactation xref , xref , xref , xref ."

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"Short term incubation (< 60 min) of prolactin responsive Nb2 lymphoma cells at high density selectively blocked prolactin stimulation of p42 and p44 mitogen activated protein kinases and transcription factors Stat1 and Stat3 but not prolactin activation of Stat5 or the tyrosine kinase Jak2."

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"This synergism could be mediated by the formation of a complex between PRL-activated STAT5 and the glucocorticoid receptor that stimulates milk-protein gene transcription, as has been reported by Stöc[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Paradoxically, cell culture studies also suggest a positive role of Shp2 in promoting prolactin stimulated Stat5 activation."

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"We demonstrated that IL-3, EPO, and PRL activated a transcription factor related to the mammary transcription factor STAT5 but not to STAT1, -2, -3, or -4 as opposed to interferon gamma (IFN gamma) which activated STAT1 in the same cells."

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"As expected, acini formed under PRL and EGF co-treatment were deprived of β-casein expression in agreement with our previous data showing a negative crosstalk between PRL and EGF by which EGF blocks PRL-induced STAT5 activation of the β-casein gene promoter, whereas PRL blocks EGF-induced MEC growth [63] (Fig. S1)."

sparser
"We therefore determined whether PTP1B up-regulation in breast cancer might represent a mechanism that reduces sensitivity of the Stat5 pathway to prolactin by investigating the effect of PTP1B knockdo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Instead, we demonstrate that prolactin activation of Stat5 results in the formation of a complex between phospho-Stat5 and BRCA1 that inhibits the function of BRCA1 at the p21 promoter.All cell lines [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"We studied the mechanisms involved in the prolactin activation of Stat5 in COS cells co-transfected with cDNA encoding Stat5 and the prolactin receptor."

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"Prolactin treatment of the transfected cells caused activation of Stat5 within 5-10 min."

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"Consistent with previous results, prolactin activated Stat5 whereas S179DPRL did not ( Fig. 7 , showing examples of T47D and PC3 cells with endogenous high and low expression of PRLRs, respectively)."

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"Similarly, PRL and EPO activated a STAT5 like factor (STAT5-L) in the rat Nb2 and the human UT7 cells expressing endogenous PRL and EPO receptors, respectively."

sparser
"In mammary gland epithelial cells activation of STAT5 by prolactin stimulates expression of milk protein genes [2] ."

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"In particular, AR engages in a transcriptional cooperation with prolactin activated Stat5 and Runx2 to regulate PIP expression [8,9]."

sparser
"Coinjection of female Balb-c/J mice with Δ1–9 and exogenous prolactin reduced the prolactin-induced activation of STAT3 and STAT5 but only at an antagonist/prolactin ratio of 100:1."

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"We have shown that the STAT5 dependent immediate early gene, CIS1 (Cytokine Inducible SH2 domain containing protein-1), suppresses PRL induced STAT5 activation in vitro as well as in transgenic mice."

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"Interestingly, Y532 has been shown to be unnecessary for STAT5 activation, although CIS1 overexpression suppressed PRL induced STAT5 activation."

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"First, administration of PRL, but not GH or epidermal growth factor, uniformly enhanced basal activation of Stat5 in luminal mammary epithelial cells."

sparser
"Rather PRL activation of Stat5, principally Stat5b, occurred in association with luteinization."

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"A ligand induced mechanism for activation of Stat5 in prostate cancer was suggested by the ability of prolactin (Prl) to stimulate activation of both Jak2 and Stat5 in CWR22Rv human prostate cancer cells and in CWR22Rv xenograft tumors."

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"In addition, Prl restored constitutive activation of Stat5 in five of six human prostate cancer specimens in ex vivo long-term organ cultures."

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"Here we demonstrated that the physical stiffness (elastic modulus) of the ECM, but not collagen I ligand density, controls PRL induced signals to the pro tumorigenic FAK/SFK/ERK1/2 signaling pathway, with only modest effects on PRL induced STAT5 signals."

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"One example of a positive interaction is the synergistic activation of beta-casein gene expression in the mammary gland, mediated by a direct physical interaction between prolactin activated STAT5 and the GC receptor, which is activated by GCs [XREF_BIBR]."

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"Prolactin and glucocorticoid activate the STAT5 and GR pathways, respectively, and induce lactation-specific TJ formation in addition to milk production in MECs [44]."

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"These data reveal that it is the accessibility of the receptor to apically added ligand that limits Prl induced STAT5 activation in monolayer cultures."

sparser
"We found that PRL activates STAT-5 in human CB CD34 + cells."

sparser
"To the best of our knowledge, this is the first observation of STAT-5 activation by PRL in nontransformed, human hematopoietic cells."

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"Thus, our data show that beta1 integrin is critical for the Prl induced activation of Stat5, a transcription factor essential for mammary epithelial differentiation, and they provide genetic evidence for cooperation between integrin and cytokine signaling pathways."

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"In DG-/- cells, Prl failed to induce the sustained activation of STAT5 even in the presence of lrECM (XREF_FIG)."

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"Our finding that there is no or limited accessibility of the basolaterally localized PrlR to its ligand in the apical space solves the puzzle of why Prl fails to induce STAT5 activation in mammary epithelial cells cultured on 2D surfaces."

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"Furthermore, we have shown for the first time that decidual PRL may act locally to activate the Jak2 and Stat5 pathway and up-regulate important genes involved in decidual growth and placentation."

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"In contrast to the role of NOTCH, activation of Janus kinase 2 (JAK2) and STAT5 by prolactin leads to alveolar differentiation and beta-casein production 37."

sparser
"Although it is known that PRL activates STAT5, it remains to be determined which factors activate STAT3 in the mammary gland and whether this is important for growth and apoptosis."

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"GH and prolactin (PRL) are potent activators of STAT5 and exert adipogenic and antiadipogenic effects in adipocytes."

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"The co-structure led to accumulation of PI(4,5)P at the TMD interface and mutation of residues identified to specifically interact with PI(4,5)P negatively affected PRL-induced STAT5 activation."

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"Indeed, STAT5 is activated by prolactin (Prl) XREF_BIBR in ARC dopamine neurons XREF_BIBR, XREF_BIBR, and by GH in somatostatin neurons XREF_BIBR."

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"However, we have reported that in human breast cancer cell lines Jak1 is also recruited in a Jak2 dependent manner for maximal PRL activation of Stat5 and other signaling mediators [XREF_BIBR]."

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"Prolactin strongly activates STAT5 and MAPK signaling in rat and human myometrial cell lines."

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"Prl stimulation of the cells induced a robust dimerization of Stat5, and this was inhibited equally by both IST5 and IST5-M at IC50 of approximately 1.3 muM (XREF_FIG C)."

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"We previously showed that an ILK-Pix-Rac signalling axis is of critical importance to Prl induced STAT5 activation and milk protein production."

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"Prolactin (Prl) activation of STAT5 is necessary for casein gene expression."

sparser
"However, when cells were grown either on a nonadhesive substratum with LN1 or on top of 3D lrECM gels, Prl was able to bind to the exposed receptor and could activate STAT5 transiently."

sparser
"In comparison to the MCF-7 clone 146D hi , the levels of constitutive or PRL-induced STAT5 activation observed in all MDA-MB231 clones were much lower ( Fig. S6A )."

sparser
"RU 486 was not able to cause an increase in transcription of the β-casein promoter construct over that observed with prolactin activated Stat5 alone."

sparser
"Be cause the predominant form of PRL receptors expressed in Nb2 cells lacks an internal segment of 198 amino acid residues (Ali et al., 1991), our results with this cell line suggested that con[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

eidos
"STAT5 is activated by prolactin and is essential for both mammary development and milk production ."
| PMC

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"Immunoprecipitation of individual STAT proteins with specific antisera followed by antiphospho tyrosine immunoblotting showed that PRL treatment of both cell lines induced marked tyrosine phosphoryla [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"This selective activation of STAT5 by prolactin was also observed in COS-7 cells cotransfected with the long form of the mouse prolactin receptor (PRL-R) and expression vectors for STAT1, STAT3, STAT5 and STAT6."

sparser
"The prolactin-activated transcription factor STAT5 binds to tandem sites that coincide with activating histone enhancer marks and additional transcription components."

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"Based upon these observations, we conclude that PRL receptors are able to activate STAT1, STAT3 and STAT5 also in myeloid 32D cells, suggesting that these three STATs are widely used mediators of PRL [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Retracted: PRL/PRLR Can Promote Insulin Resistance by Activating the JAK2/STAT5 Signaling Pathway."

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"Western blot analysis showed that Stat5 is induced by PRL to translocate into the nucleus."

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"The experiment shows that prolactin is able to activate STAT5 in SKBR3 cells in a dose dependent manner."

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"Stat5 chromatin immunoprecipitation demonstrated physical interaction with a BCL6 gene regulatory region, and BCL6 transcript repression required histone deacetylase activity based on sensitivity to trichostatin A. Functionally, BCL6 overexpression disrupted prolactin induction of Stat5 reporter genes."

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"A mouse model of Stat5 activation by Prl recapitulates prostate tumorigenesis from precancerous lesions to invasive carcinoma [75] ."

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"Mechanistically, PRL induces mammary lactogenic differentiation via the downstream activation of Janus kinase 2 (Jak2) and signal transducer and activator of transcription 5 (STAT5) [24,25] , and poss[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"To assess if MS-1020 has selectivity for JAK3 inhibition, we examined the effects of this compound on STAT5 signaling induced by PRL or IL-2 stimulation in Nb2 cells."

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"Prolactin stimulation of 60 minutes resulted in activation and binding of STAT5 to DNA response elements present in the beta-casein promoter."

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"Stat5 was rapidly induced by 30 min of PRL stimulation to enter the nucleus, and a significant level of Stat5 was still detectable at 10 h of PRL stimulation."

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"One important advance was the discovery of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway; prolactin (PRL)-induced activation of JAK2 and STAT5 is required to induce expression of most, if not all, milk protein genes [XREF_BIBR, XREF_BIBR]."

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"In this study, we also identified HSP90A as a prolactin induced STAT5 activated target gene."

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"Histone H1 and Chromosomal Protein HMGN2 Regulate Prolactin induced STAT5 Transcription Factor Recruitment and Function in Breast Cancer Cells."

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"Given the important role for estrogens in maternal behavior and the recent finding that PRL treatment enhances STAT5 activity in ERalpha neurons in the female mouse brain, the relationships between alterations in neural sensitivity to PRL and the apparent shift in estrogen receptor activity may play an important role in regulating enhancements of maternal care, i.e. the retention of maternal behavior, long after the cessation of lactation."

sparser
"Prolactin-activated Stat5 directly binds and functionally inhibits the BCL6 regulatory region by a trichostatin A sensitive mechanism."

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"Notwithstanding, this is the first demonstration for WAP CoRE that the transcriptionally activate form of NFI not the repressor form is glycosylated.We previously proposed a working hypothesis that th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"GH and prolactin (PRL) are potent activators of STAT5 and exert adipogenic effects in preadipocytes."

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"Following the finding that LLP-A expression is dependent on PRL [10] , the cloned 5′-flanking region for this gene was analyzed for binding sites of the PRL-activated Stat5."

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"Prolactin (PRL) is the key activator of STAT5 in mammary tissue and its level rises during pregnancy followed by a sharp drop at the end of lactation."

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"PRL stimulation of these cells also resulted in Stat5 activation suggesting the presence of a functional PRL pathway in this cellular model of TNBC-PRLR subgroup."

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"Whereas the prolactin-activated transcription factor STAT5, which covers two highly homologous proteins, STAT5a and STAT5b, is essential for the development and differentiation of the mammary gland as[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Receptors for IL-2, IL-3, IL-4, IL-5, IL-7, IL-9, IL-15, GM-CSF, erythropoietin, thrombopoietin, growth hormone, prolactin, and SCF all activate Stat5 (Leonard and O'Shea, 1998)."

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"Predictably, the ability of PRL to activate Stat5 and AP-1 was inversely related in mammary cell lines."

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"SOCS2 suppresses PRL mediated STAT5 activation and forms a negative feedback loop in mammary epithelium."

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"Consistent with this, p100 has been shown to interact with at least three other transcription factors: the differentiation-associated transcription factor, c-myb [2] , the IL-4 activated latent trans[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Furthermore, STAT5 can be activated in a JAK2-dependent manner by prolactin (PRL), growth hormone (GH), erythropoietin (EPO) and granulocyte-macrophage colony-stimulating factor (GM-CSF) [ xref ]."
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sparser
"PRL-induced tumors display inverse Stat5 and AP-1 activation and elevated epithelial pAKT."

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"Although both the long and short receptor forms have been shown to dimerize and activate JAK2, only the long PRL receptor splice form is able to activate STAT5 ( Ling et al., 2000; Swaminathan et al.,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"This study demonstrated that STAT5 can be activated by prolactin in mammary glands."

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"Overall, more research is needed to evaluate NF1-C2 and other pathways activated by prolactin in the postmenopausal, low hormone context.In addition to STAT5, the other STAT family member activating commonly in breast cancer is STAT3 [32]."

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"To initiate milk production, mammary glands require activation of STAT5 by prolactin [XREF_BIBR]."

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"Prolactin, a polypeptide hormone that activates JAK2 and STAT5 signaling pathway has been shown to improve motor function and modestly increase the lifespan of Delta7 SMA mice (XREF_FIG) [XREF_BIBR]."

sparser
"The hormone prolactin can activate Stat5, which in turn increases SMN expression (Farooq et al, xref )."

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"We conclude that BCL6 disrupts prolactin induction of Stat5 regulated reporter genes in both T47D and MDA-MB-231 cells."

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"However, unlike intact SF1b, ΔS2SF1b does not hetero-dimerize with the LF PRLR and does not inhibit PRL-stimulated Stat5 activation at the LF PRLR."

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"To test the system further, we examined Stat5 activation in response to PRL (15 min at 100 ng/ml) with and without prior induction of ΔS2SF1b for 24 h. Panel B of Fig. 5 shows that induction of ΔS2SF1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"When expressed from an adenoviral vector, PRLR1-242 inhibits activation of STAT5 (signal transducer and activator of transcription 5) by prolactin in T47-D breast cancer cells, and blocks the ability of prolactin to induce proliferation in these cells."

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"We also compared the ability of intact SF1b and ΔS2SF1b to act as dominant negatives for PRL stimulation of a multiple Stat5 response element-luciferase construct."

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"Short term incubation (<60 min) of prolactin-responsive Nb2 lymphoma cells at high density selectively blocked prolactin stimulation of p42/p44 mitogen-activated protein kinases and transcription factors Stat1 and Stat3 but not prolactin activation of Stat5 or the tyrosine kinase Jak2."

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"When instead cells were transfected with the luciferase construct and an intact SF1b vector (i.e. not ΔS2SF1b), the ability of PRL to stimulate activity of the Stat5 promoter was blocked."

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"Effect of S1b D1 subdomain mutation on prolactin stimulated Stat5 signaling mediated by LF."

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"PRL induced activation of STAT5 in human mammary epithelial cell lines has been previously reported [30]."

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"By examining the ability of pre-expression of ΔS2SF1b to affect acute (15 min) PRL activation of Stat5 at the LF, and chronic (48 h) PRL activation of a response element with multiple Stat5 binding si[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Interestingly, PRL signals to STAT5 are inversely related to its ability activate an AP-1 enhancer in a panel of breast cancer cell lines [ xref ], and the stiffness of the matrix in 3D cultures inversely modulates PRL-activated STAT5 and ERK1/2 [ xref ]."

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"The authors propose that in late pregnancy STAT5 is activated by this autocrine source of prolactin as endocrine levels are very low at this stage."

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"The data present here and in previous studies suggests that prolactin induced STAT5 activation is necessary but not sufficient for alveolar formation but is necessary and sufficient for milk production."

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"PRL triggers activation of Jak2 kinase which phosphorylates the PRL receptor itself and the mammary gland factor, Stat5, a member of the family of signal transducers and activators of transcription (Stat)."

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"In addition, Prl is known to modulate various downstream signaling pathways which include the Janus kinase/signal transducer and activator of transcription (JAK2/STAT5), MAPK extracellular regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) [60,61]."

sparser
"These data reveal that it is the accessibility of the receptor to apically added ligand that limits Prl-induced STAT5 activation in monolayer cultures."

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"PRL induced activation of Stat5 was abolished in 293 fibroblasts expressing PRL receptor mutants lacking all intracellular tyrosines."

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"Taken together, those data suggested that the PRLR/STAT5 signaling activated by PRL might be involved in maintaining and regulating the functions of the scented glands in the muskrats.The present study demonstrated that PRL, PRLR and STAT5 were expressed in the scented glands of the muskrats and there was higher concentration of PRL in the scented glandular tissues during the breeding season."

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"STAT5 is activated by prolactin and is essential for both mammary development and milk production."

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"We have previously shown that prolactin activation of Stat5 causes it to form a complex with BRCA1 that prevents BRCA1 from transactivating the p21 promoter [XREF_BIBR]."

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"Indirect immunofluorescence microscopy was used to demonstrate that PRL activated STAT5 can translocate GR into the nucleus, and that ligand bound GR can translocate STAT5 into the nucleus."

eidos
"Prl is known to activate STAT5 in cultured cells and our results indicated that Prl receptor antagonists could block this activity ."

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"Not only has this work elegantly and conclusively shown that the PI3K and Akt pathway induces autocrine prolactin production which is required for the initiation of lactation, but it has the additional merit of the use of genetically altered mouse models to study the activation of STAT5 by prolactin in vivo in the correct cellular environment so we can be confident that the data are biologically relevant."

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"In summary, results of this investigation indicate that although PRL can activate the JAK2 and Stat5 system in the corpus luteum, the down regulation of 20alpha-HSD mRNA by PRL does not appear to involve tyrosine kinase activity but depends on de novo synthesis of protein (s)."

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"Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects."

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"It is known that PRL receptors couple via Janus kinase (JAK) to signal transducer and activation of transcription (STAT) proteins, in particular STAT5, which is required in almost all mammary responses by PRL (Teglund et al., 1998)."

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"PRL treatment, alone or in combination with Pg, had no effect on the level of STAT5 expression, but inhibition of pituitary PRL secretion prevented nuclear translocation of STAT5."

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"These results indicate that oestrogen and Pg co-operatively maintain STAT5 expression in the mammary gland, while PRL induces STAT5 transcriptional activity."

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"For example, prolactin induces expression of SOCS1 [36] and in turn, SOCS1 suppresses prolactin induced STAT5 dependent gene transcription and act as a negative regulator of prolactin signaling [37]."

sparser
"Prolactin-induced STAT5 activation resulted in an invasion-suppressive phenotype, including an increase in E-cadherin expression and reduced invasion through Matrigel ( xref )."

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"Thus, mammary development and function depend on prolactin induced activation of STAT5 and on an increased concentration of STAT5 during pregnancy."

sparser
"Conversely, in a recent work, it was proposed that the cytoplasmic tyrosine phosphatase Shp2, may have dual functions in regulating STAT5 activity in the mammary gland, first acting as a positive regu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"As expected, prolactin induced STAT-5 activation."

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"There are two very similar STAT5 isoforms, termed STAT5a and STAT5b, which are selectively activated by prolactin in specific tissues."

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"The withdrawal of prolactin-induced STAT5 signaling results in a surge in IL-6 and LIF levels, activating the gp130 receptor and initiating LIF-induced STAT3 signaling, a pivotal event in this stage [65]."

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"STAT5 is primarily activated by IL-2, granulocyte-macrophage CSF (GM-CSF), IL-15, IL-7, IL-3, IL-5, and prolactin (PRL) and regulates the expression of pro-growth and pro-survival genes."

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"Thus, PRL only minimally activates Stat5 in rat liver (Waxman et al., 1995; LeStunff et al., 1996) Similarly GH will not replicate PRL 's ability to initiate transcription of a beta-casein reporter ge[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"However, in MCF-7 cells, the prolactin-induced STAT5 signalling is weaker than in T47D cells, and these cells exhibit distinct molecular characteristics ."

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"In turn, Prl alone enhances STAT5 occupancy on both the promoter and BCE, without any appreciable induction of transcription, and this occupancy is further stabilized by the addition of Gc."

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"Elegant knockout experiments in mice demonstrated that loss of either dystroglycan or β1 integrin leads to aberrant tissue architecture which was accompanied with a loss in STAT5 signaling and β-casein production induced by PRL (Leonoudakis et al., 2010; Naylor et al., 2005)."

sparser
"As shown in Fig. 4 b, prolactin activated STAT-5 equally well in control cells and in STAT-3 i HC11 cells, indicating that down-regulation of STAT-3 did not affect expression and activation of STAT-5."

reach
"Others have shown that integrin-linked kinase (ILK) couples β1 integrin to Rac1, promoting PRL-induced STAT5 activation and, eventually, β-casein gene expression (Akhtar et al., 2009)."

reach
"In our study, PRL, PRLR, and STAT5/pSTAT5 were localized in luteal cells of wild ground squirrels during the breeding season, implying that the PRLR/STAT5 pathway, activated by PRL, might play a role in maintaining and regulating ovarian luteal function."

reach
"IGF-I stimulates DNA binding activity of one of the key transcription regulators of casein genes: STAT5 (signal transducer and activator of transcription 5), which belongs to the Janus kinase—signal transducer and activator of transcription pathway (JAK2/STAT5 pathway) stimulated by prolactin [60]."

reach
"PRL-induced Stat5 activation is associated to high-grade prostate tumors and aggressiveness, and PRLR inhibition reduced tumor burden [3, 4]."

sparser
"How oleic acid enhances prolactin-induced STAT5 activation, while alone has no effect on STAT5 activation, is unclear."

reach
"As a validation of the system [24], PRL wt induced the transcriptional activation of Stat5-regulated genes (CISH promoter activity), in contrast to PRL mut that failed to induce any transcriptional activity (Fig. 3B)."

reach
"To understand the intrinsic effect of 17beta-estradiol (E2) and ICI on expression of the STAT5 isoforms and how these outcomes affect the interplay with PRL activated STAT5 isoforms in mammary epithelia of differing phenotypes, we compared the well characterized, differentiated HC11 mouse cell line [XREF_BIBR] and ERalpha + mouse mammary tumor cell (TC) lines generated from PRL induced adenocarcinomas [XREF_BIBR]."

reach
"MCF7 cells represent another luminal breast cancer cell line with relatively high levels of prolactin receptors but with generally weaker prolactin induced Stat5 signaling than T47D cells."

reach
"Interestingly, PRL but not GH activated Stat5 in nearly all of the endocrine glands."

reach
"Prolactin induces MECs to produce milk by activating the signal transducer and activator of transcription 5 (STAT5)/Janus kinase 2 (JAK2) pathway [ 9 , 10 ]."

reach
"In mammary glands, PRL activated Stat5 in a majority of luminal epithelial cells but not myoepithelial cells, stromal fibroblasts, or adipocytes, whereas GH activated Stat5 in a significant fraction of myoepithelial cells, fibroblasts, and adipocytes but only in a minority of luminal cells."

reach
"Prolactin and glucocorticoids respectively activate STAT5 and GR signaling to induce milk production in MECs during lactation [ 26 , 37 ]."

sparser
"STAT5A-induced PRL in the conditioned medium can activate STAT5, STAT1, and to a lesser extent STAT3 in hCMEC/D3 cells, suggesting the existence of a positive feedback loop between STAT5 and PRL that promotes angiogenesis."

reach
"As an example, interleukin 6 (IL-6) and prolactin (PRL) generally activate STAT3 and STAT5, respectively, in relevant cell types to up-regulate transcription of target genes (DaSilva et al., 1996; Hir[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Since it is well established that PRL activates Stat5 through the tyrosine kinase, Janus kinase 2 (Jak2), the role of Jak2 in PRL regulation of ERalpha expression was investigated."

reach
"Accordingly, we find that PRL robustly activates STAT5 and MAPK signaling in the rat leiomyoma cell line ELT3."
| PMC

reach
"In addition, Prl induced Stat5 activation increased Jak2 mRNA levels by 80-120% in PC cells, which was blocked by genetic knockdown of Stat5 by shRNA (XREF_FIG, XREF_FIG)."

reach
"PRL increases beta-cell proliferation through phosphorylation and activation and enhanced nuclear localization of STAT5."

reach
"XREF_BIBR, XREF_BIBR However, in the absence of ECM protein, prolactin induces transient STAT5 activation but fails to activate milk protein expression."

sparser
"Whereas the prolactin-activated transcription factor STAT5, which covers two highly homologous proteins, STAT5a and STAT5b, is essential for the development and differentiation of the mammary gland as[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"PRL activates the Jak2/STAT5 pathway via the PRL receptor and includes Jak2 activation followed by STAT5 phosphorylation [[11], [12], [13], [14]]."

sparser
"We identified that PRL activates STAT5, m-TOR and MEK and induces cell proliferation in FTE cells."

reach
"Four hours after cloprostenol administration, the corpus luteum was refractory to stimulation of STAT5 by PRL administration, and this was not due to down-regulation of PRL receptor."

sparser
"These enhancers are occupied by the prolactin-activated transcription factor STAT5 and additional regulatory factors, including RNA polymerase II."
| PMC

sparser
"STAT5 is activated by prolactin and is essential for both mammary development and milk production."
| PMC

reach
"This transitional population of MCH neurons during lactation is modulated by prolactin ( Kokay et al., 2020 ), and most MCH neurons coexpress the prolactin-induced phosphorylated signal transducer and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"To facilitate and sustain the production of milk, PRL necessitates interaction with its receptor, known as the PRL receptor (PRLR), which subsequently activates the Jak2/Stat5 signaling pathway [ 34 ][MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In T47D cells, the PRL induction of PTHrP transcript was further enhanced by the overexpression of Stat5, either basal or PRL-induced, thus supporting the Stat5-mediated regulation of PTHrP ( Sato et [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"In T-47D cells, PRL-induced Stat5 activation could inhibit MMP expression at physiological concentrations ( Philips and McFadden, 2004; Sultan et al., 2005 )."

reach
"The activation of ERalpha decreases the PRL induced STAT5 transcriptional activity."

sparser
"Thus, mammary development and function depend on prolactin-induced activation of STAT5 and on an increased concentration of STAT5 during pregnancy."

reach
"The mechanisms by which GH and PRL promote β-cell proliferation and gene expression, and the role of Stat5 have been explored in vitro [7–9] ."

reach
"Similar C/EBPbeta, C/EBPdelta, STAT5, and Prl activated STAT5 were found under all culture conditions."

sparser
"The PRL-induced STAT5 activation was significantly decreased in cells expressing either the K4G, K4E, or the φ4G variants, whereas STAT5 activation in cells expressing the GAG variant was not significantly different from that of WT expressing cells ( xref )."

reach
"STAT5 is activated by prolactin, erythropoietin and growth factors [ 95 ]."

sparser
"To determine whether Src was required for PRL-induced activation of STAT5 and expression of β-casein we utilized primary mammary epithelial cells (MECs) isolated from the mammary glands of Src -/-, Src +/-, and Src +/+ mice."

reach
"Additionally, prolactin activates the signal transducer and activator of transcription factor (STAT5) pathway, exclusively the STAT5b isoform in the brain (60)."

reach
"To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin induced STAT5 activation."

reach
"Another member of STAT family, STAT5, which is induced by prolactin and growth hormone is also involved in regulation of tumor cell proliferation."

sparser
"We previously showed that an ILK-Pix-Rac signalling axis is of critical importance to Prl-induced STAT5 activation and milk protein production."

sparser
"Taken overall, our findings demonstrate that GH and PRL activate Stat5 in separate compartments, which in turn reflects their specific role in ductal and alveolar development and differentiation ( Gal[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Further research is needed to explore the biological interactions between PRL-induced Stat5 signaling and PTHrP in breast cancer cells."

reach
"Although PRL is a known activator of STAT5 in the mammary gland, these data showing ErbB3 dependent induction of STAT5 expression, taken with previous data demonstrating ErbB4 mediated phosphorylation and activation of STAT5, suggest that NRGs produced locally in the mammary microenvironment enable PRL mediated STAT5A activation, while at the same time promoting PI3K and Akt signaling, which together amplify, sustain, and differentiate this unique cell population on which newborn mammals depend."

reach
"XREF_BIBR, XREF_BIBR Moreover, we previously showed that Prolactin promotes cardiac STAT5 activation."

reach
"Acute injection of Prolactin (400IU/kg) strongly induced activation of STAT5 in WT-NP mice and in CKO-NP mice (STAT5 activation after Prl treatment : WT Prl : 5,5-fold, CKO Prl : 4-fold vs. WT NaCl, ** P < 0.01, n = 6)."

reach
"Direct injection of Prolactin activated STAT5 in both genotypes further explaining how sRlx via Prolactin and STAT5 activation could induce cardiomyocyte growth in both genotypes."

sparser
"In the mammary gland, prolactin-activated STAT-5 increases GR binding to the β-casein promoter ( Wyszomierski et al., 1999 ), whereas in lymphocytes, IL-2-regulated STAT-5 activity decreases GR bindin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In comparison to the MCF-7 clone 146D hi, the levels of constitutive or PRL induced STAT5 activation observed in all MDA-MB231 clones were much lower."

reach
"Stat5 can be activated in these cells by Prl stimulation (XREF_FIG a)."

reach
"Prolactin stimulation of beta-casein and WAP was also suppressed, further confirming functional knockdown of STAT5 in the HC11/4ICD cells."

sparser
"Despite RANKL/NF-κB/ Cyclin D1 axis playing an important role in MECs proliferation and alveolargenesis, it has been reported that enhanced RANKL/Rank signaling affects lactogenic differentiation in MECs by inhibiting the PRL-induced activation of Stat5 and expression of Elf5 required for lactation, and that RANKL inhibition at mid-pregnancy resulted in increased Elf5 expression and activation of Stat5, leading to a premature secretory differentiation [ xref , xref ]."

sparser
"Intriguingly, STAT-5 activation by prolactin in differentiated adipocytes leads to changes in lipid metabolism that go in opposite direction of those induced by prolactin in mammary gland cells."

reach
"In human endothelial cells, PRL activates the PRL receptor (PRLR) resulting in MAPK and STAT5 activation, thus closing a positive feedback loop."

sparser
"In compliant matrices, PRL activates STAT5 and stimulates development of well-differentiated colonies."

sparser
"Following the finding that LLP-A expression is dependent on PRL [10] , the cloned 5′-flanking region for this gene was analyzed for binding sites of the PRL-activated Stat5."

reach
"These enhancers are occupied by the prolactin activated transcription factor STAT5 and additional regulatory factors, including RNA polymerase II."
| PMC

reach
"STAT5 is activated by prolactin and is essential for both mammary development and milk production."
| PMC

reach
"It remains to be seen whether the increased beta-cell replication observed in pregnancy is also achieved through this mechanism, but evidence suggests that in pregnancy, prolactin not only increases STAT5 signalling, it also reduces the levels of the tumour suppressor gene menin, which is a known inhibitor of Cdk2 activity [XREF_BIBR]."

reach
"Prolactin activates the Stat5 but not the Erk1/2 or Akt signaling pathways in medaka gill : The activation of cell signaling pathways was studied using dual labeling Western blots of lysates from meda[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Prolactin activates pSTAT5 in the supraoptic nucleus of virgin and lactating rats A–D, representative images of pSTAT5 (nuclear staining) and oxytocin immunostaining (cytoplasmic staining) in the supraoptic nucleus of virgin and lactating rats after three injections of bromocriptine over 28–4 h before the experiment."

sparser
"Whereas TGFβ/Smad signaling was found to block PRL-induced Stat5 activation, PRL/Jak2 signaling was found to suppress TGFβ/Smad activation [ xref , xref ]."

reach
"Prolactin-induced activation of Stat5 was shown to be associated with a parallel increase in ncc2b expression."

reach
"Prolactin induced Stat5 signalling is abrogated, and LIF induced Stat3 signalling is initiated, upon induction of involution."

reach
"Indeed, utilizing a previously reported set of Stat5 target genes, we found that of the 40 Stat5 target genes significantly induced by prolactin with a fold change greater than 1.2, 50% (20/40) were also significantly inhibited by Bufexamac (XREF_FIG)."

reach
"STAT5 molecules carrying K → R exchanges at K694 revealed that acetylation of particularly this site is necessary for the prolactin-induced dimerization of endogenous STAT5 [51] ."

reach
"The time course of Stat5 activation by GH, Prl and PL was also examined and exhibited a specific pattern in relation to the ligand."

sparser
"This selective activation of STAT5 by prolactin was also observed in COS-7 cells cotransfected with the long form of the mouse prolactin receptor (PRL-R) and expression vectors for STAT1, STAT3, STAT5 and STAT6."

sparser
"However, prolactin activated STAT5 in female postpartum suckling rat liver, resulting in transcriptional activation of Ntcp gene [20] ."

reach
"These data indicated that PRL normally triggered Stat5 signaling in the ventral lobe, which suggested that the lack of Stat5 activation observed in ventral lobes of Pb-PRL mice ( Figure 2 , A–C) might[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"PIKE-A is critical for the activation of Akt signaling its depletion in HC11 epithelial cells diminished PRL induced Stat5 activation and cyclin D1 expression, resulting in profoundly impaired cell pr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The time course of Stat5 activation by GH, Prl and PL was also examined and exhibited a specific pattern in relation to the ligand (Figure 5C)."

reach
"Depletion of PIKE-A in HC11 epithelial cells diminished PRL induced STAT5 activation and cyclin D1 expression, resulting in profoundly impaired cell proliferation in vitro."

sparser
"Stat5 could be activated by prolactin and its receptor, and by peptide growth factors and their receptors, e.g., HER4 has also been shown to activate Stat5 ( xref ; xref ; xref )."

reach
"Once in circulation, prolactin acts upon its receptor (PRLR) to activate secondary messenger cascades in target cells, such as the signal transducer and activator of transcription 5 (STAT5) pathway ( [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Because human growth hormone (hGH) activates Stat1, 3, 5 and human prolactin (hPRL) activates Stat5, these results show that hPL uses a unique signal transduction pathway which is different from hGH and hPRL."

reach
"However, once proper polarity has been restored by culturing the cells as LM-111 microincapsulated 3D aggregates, prolactin stimulation initiated the STAT5 activation pathway and resulted in stimuli driven beta-casein expression."

reach
"Estrogen can potentiate PRL activated Stat5 activity in some mammary cells, including some breast cancer cell lines."

reach
"Interestingly, PRL signals to STAT5 are inversely related to its ability activate an AP-1 enhancer in a panel of breast cancer cell lines [XREF_BIBR], and the stiffness of the matrix in 3D cultures inversely modulates PRL activated STAT5 and ERK1/2 [XREF_BIBR]."

sparser
"Our findings demonstrate that GH, Prl, and EGF activate Stat5 in separate compartments, which in turn reflects their specific roles in ductal and alveolar development and differentiation."

reach
"PRL and EGF synergistically induce signals to ERK1/2 and AKT, but not STAT5, and PRL also can activate HER2."

sparser
"We have used the prolactin activation of Stat5 and the transcription of a β -casein promoter luciferase gene reporter construct as a model to study the functional interaction between p53 and the cyto[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Like crosstalk downstream of PRLR and EGFR, PRL and IGF-I cooperatively activate ERK1/2 and AKT, but not STAT5."

reach
"2,12,13 However, our data indicate that acute PRL stimulation activates the same signaling pathway (Jak2/Stat5) in all three prostate lobes."

sparser
"Although the PRL-induced activation of Jak2 and Stat5 is able to regulate the levels of active Akt1 and nuclear accumulation of Cyclin D1 in normal cells ( xref ; xref ; xref ), we have demonstrated recently that the expression of constitutively active ErbB2 was sufficient to elevate the expression of these downstream mediators independently of Jak2."

reach
"The possiblity that cyclin D2 and/or D3 are regulated in T cells by the Stat5 proteins is supported by the observation that prolactin, which strongly induces Stat5 activation, induces cyclin D2 and D3[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"While Prl activated Stat5 only in the epithelium, GH and EGF activated Stat5 preferentially in the stroma."

reach
"EGFR, independent of PRL/PRLR, can activate STAT5 indirectly via c-SRC and drive the expression of target genes involved in cell proliferation and survival."

reach
"It is well known that PRL and GH are important modulators of lipid metabolism and are also potent inducers of STAT5 in adipocytes [XREF_BIBR, XREF_BIBR]."

reach
"Our data indicate that in the mammary gland CIS and SOCS3 are involved in regulating STAT5 signaling at three different instances : 1) SOCS3 serves as a mediator of the inhibitory EGF effect on PRL induced STAT5 activation; 2) CIS and SOCS3 play a role as negative feedback inhibitors of PRL action; 3) Inhibition of CIS and SOCS3 expression by glucocorticoids contributes to the positive effect of glucocorticoids on PRL induced STAT5 activation."

sparser
"Activation of Stat5 by prolactin in COS7 cells has no influence on the transactivation of p53-dependent reporter construct by p53."

reach
"Canonical STAT5 signal transduction is initiated by binding of prolactin to the receptor, which activates transient JAK2 mediated phosphorylation and nuclear translocation of STAT5."

reach
"Induction of milk synthesis by the alveolar cells occurs during pregnancy in response to prolactin mediated activation of Stat5."

reach
"In addition, MS-1020 suppressed IL-2-induced JAK3 and STAT5 activation but not prolactin stimulated JAK2 and STAT5 signaling in rat T-lymphocyte Nb2 cells."

reach
"Since Stat5 was initially purified and its cDNA cloned as mammary gland factor, a PRL inducible transcription factor involved in regulating milk protein gene expression in the lactating mammary gland [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Furthermore, STAT5 can be activated in a JAK2-dependent manner by prolactin (PRL), growth hormone (GH), erythropoietin (EPO) and granulocyte-macrophage colony-stimulating factor (GM-CSF) [60]."
| PMC

sparser
"Therefore, STAT5 activation by PRL is indispensable for initiating β-casein expression."

reach
"(1995) fnterleukin-3, erythropoietin, and prolactin activate a STAT5 like factor in lymphoid cells."

reach
"Second, beta1 integrins are actively required for Prl signaling both in culture and in vivo because function perturbing anti-beta1 integrin antibodies block MEC differentiation, a dominant negative (DN) beta1 integrin transgene compromises Stat5 activation and milk production, and Prl can not activate Stat5 in beta1 integrin-null MECs."

reach
"All of these reporters commonly carry one or more Stat5 responsive elements and have been widely used to study the PRL induced activation of Stat5 pathway."

reach
"Prolactin exposure induces JAK2/STAT5 signaling in placental cells."

reach
"In a separate assay to quantify the percentage of cells in which Prl induced Stat5 translocation to the nucleus, monolayer cultured cells were differentiated by adding diluted BM matrix to the culture medium (i.e., 2D culture with BM overlay) before stimulation with Prl for 15 min."

sparser
"Activation of Stat5 through the prolactin receptor by either PL or prolactin in β-cells of pregnant rodents can down-regulate the tumour suppressor gene menin 1, resulting in inhibition of the cell cy[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Activation of Stat5 by PRL in human breast cancer lines was associated with increased surface levels of the invasion-suppressive adhesion molecule E-cadherin in vitro and in xenotransplant tumors in vivo."

reach
"PRL activates the latent cytoplasmic Stat5 by tyrosine phosphorylation and dimerization in PRL/Jak2/Stat5 pathway [XREF_BIBR]."

reach
"These findings suggest that PRL robustly activates the JAK2/STAT5 pathway at the maternal-fetal interface, potentially through targeted reduction of SOCS1 and/or SOCS2 expression."

reach
"The present study of prolactin (PRL) receptor mediated recruitment of signal transducers and activators of transcription (STATs) demonstrates that PRL activates STAT3, in addition to STAT1 and STAT5 as previously reported, and that STAT1, STAT3 and STAT5 are mediators of PRL effects in cells whether of lymphoid, myeloid or mammary epithelial origin."

sparser
"Indirect immunofluorescence microscopy was used to demonstrate that PRL-activated STAT5 can translocate GR into the nucleus, and that ligand-bound GR can translocate STAT5 into the nucleus."

sparser
"Prolactin activates pSTAT5 in the paraventricular nucleus of virgin and lactating rats A–D, representative images of pSTAT5 (nuclear staining) and oxytocin immunostaining (cytoplasmic staining) in the paraventricular nucleus of virgin and lactating rats after three injections of bromocriptine over 28–4 h before the experiment."

reach
"Retinoic acid modulates prolactin receptor expression and prolactin induced STAT-5 activation in breast cancer cells in vitro."

sparser
"STAT5 is activated by prolactin, erythropoietin and growth factors [ 95 ]."

sparser
"For ex- ample, erythropoietin, prolactin, growth hormone, and IL2 all trigger the phosphorylation and activation of STAT5."

sparser
"In mammary glands, PRL activated Stat5 in a majority of luminal epithelial cells but not myoepithelial cells, stromal fibroblasts, or adipocytes, whereas GH activated Stat5 in a significant fraction of myoepithelial cells, fibroblasts, and adipocytes but only in a minority of luminal cells."

reach
"This might suggest that most cancer cells had lost the PRL mediated autocrine activation of its downstream mediator Stat5 in the progressing lesions (XREF_FIG)."

reach
"Constitutive expression of SOCS-1 and SOCS-3 suppressed PRL induced STAT5 dependent gene transcription."

sparser
"In the developing breast, STAT5 is activated by prolactin (mainly) and other signaling pathways, such as hormonal receptors and EGFR, and promotes its’ terminal differentiation and lactation [26] ."

reach
"In this study we demonstrate that PRL also induces the binding of STAT5 proteins to the rat insulin-1 STAT5 motif."

reach
"Although it is known that PRL activates STAT5, it remains to be determined which factors activate STAT3 in the mammary gland and whether this is important for growth and apoptosis."

reach
"Prolactin can activate the STAT5/JAK2 pathway to increase milk fat synthesis in mammary gland ( Hennighausen et al., 1997 )."

reach
"During lactation, prolactin can activate the STAT5/JAK2 pathway to increase milk fat synthesis ( Dentelli et al., 2009 )."

sparser
"PRL induced activation of STAT5 in human mammary epithelial cell lines has been previously reported [30] ."

reach
"The STAT5 signaling pathway, considered essential for luteinization and progesterone production, was activated by PRL in both transgenic mice models."

sparser
"It has recently been shown that activation of Stat5 by PRL stimulates 3β-HSD type 2 transcription and this effect was dependent on the Stat5 binding element [3] ."

sparser
"Of particular interest for premenopausal breast cancer, PRL-activated STAT5 suppressed a progestin-induced progenitor population in T47D breast cancer cells ( xref )."

sparser
"For example, the lactogenic hormone complex of prolactin and glucocorticoids (HP) respectively activate STAT5 and glucocorticoid receptor (GR) transcription factors."

reach
"Prolactin signals through its receptor, activating the Jak2–Stat5 pathway."

reach
"In addition, rapamycin did not affect PRL stimulation of Akt or Stat5."

reach
"PRL stimulates the Jak and Stat pathway (Jak2 and Stat5) in the mammary gland, which is responsible for the induction of milk protein expression in BMEC as well as other mammary epithelial cells due to the presence of Stat5 binding sites on the epithelial cells, and this could be a potential regulatory pathway by which 5-HT acts through 5-HT 2A."

reach
"In the presence of laminin-111, prolactin treatment induced sustained STAT5 activation in mammary epithelial cells cultured in suspension, which leads to transcription of beta- and gamma-casein genes."

reach
"In T47D, sol IGF-1R inhibited neither GH- nor PRL induced STAT5 activation."

reach
"STAT5 is predominantly activated by PRL during gestation."

reach
"PRL activated MAPK and STAT5 signaling in human myometrial cell lines and promoted myofibroblast trans-differentiation which in turn contributed to leiomyomas fibrosis."

sparser
"In breast cancer cells, Prolactin (PRL) induced activation of FAK and Stat5 is mediated via Src family kinases."

sparser
"STAT5 is predominantly activated by PRL during gestation."

reach
"Thus, proliferation may be increased by both enhanced PRL-induced STAT5 signalling and constitutive Akt signalling."

sparser
"PRL activates the latent cytoplasmic Stat5 by tyrosine phosphorylation and dimerization in PRL/Jak2/Stat5 pathway [ xref ]."

reach
"Others have shown that PRL, through JAK2, induces binding of STAT5 to a distal GAS site in the cyclin D1 promoter, thereby enhancing promoter activity in Chinese hamster ovary (CHO-K1) cells transfected with the long form (LF) of PRLR [XREF_BIBR]."

sparser
"STAT5 pathway activation by PRL in these experiments is evident in regulation of multiple STAT5 target genes, including the immune system modulating genes and pathways: IL-2, IL-3 and Bcl-2 signaling, Il2ra , Tnfsf10 , Foxp3, Slfn2, C3ar1, Osm, Socs1 , etc. ( xref ; xref ; xref ) (Supplementary Excel files/material)."

reach
"PRL induced the expected rapid activation of STAT5 (within 15min, results not shown), and T47D cells were therefore treated with PRL for 15min to assess the effect of knocking down JAK2, STAT3, and STAT5A on LKB1 transcriptional activity."

reach
"The role of CTGF and CCN2 in lactogenic differentiation may depend on its function in the expression and stabilization of matrix-integrin complexes, an activity which promotes prolactin induced Stat5 activity."

reach
"41 In addition, SOCS7 can modulate the JAK‐STAT signalling pathway induced by leptin and prolactin via the interaction of JAK2‐STAT3 and JAK2‐STAT5."

sparser
"Thus, PRL only minimally activates Stat5 in rat liver ( Waxman et al., 1995; LeStunff et al., 1996 ) Similarly GH will not replicate PRL’s ability to initiate transcription of a β-casein reporter gene[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Both Stat5s can be activated by prolactin, growth hormone, erythropoietin and granulocyte-macrophage colony stimulating factor ()."

reach
"In summary, prolactin and oleic acid synergistically stimulate islet cell proliferation and islet growth in rat islets, oleic acid increases prolactin induced STAT5 activation, and requires both the metabolism of oleic acid and non metabolized oleic acid."

reach
"In vitro expression of long and short ovine prolactin receptors : activation of Jak2 and STAT5 pathway is not sufficient to account for prolactin signal transduction to the ovine beta-lactoglobulin gene promoter."

reach
"It has been shown that PRL induced activation of MAPK/AP -1 pathway is inversely related to PRL induced STAT5 activation [XREF_BIBR - XREF_BIBR]."

reach
"In the AP-grafted groups in the current study, JAK2 and STAT5 were transiently activated by elevated PRL levels after 7 days of IH treatment."

sparser
"The prolactin-activated transcription factor STAT5 binds to tandem sites that coincide with activating histone enhancer marks and additional transcription components."
| DOI

reach
"Its ectopic expression enhances PRL induced Stat5 mediated transcriptional activation."

reach
"SOCS3 represses and modulates the activity of STAT5, inhibiting PRL induced milk synthesis (Haricharan and Li, 2014), but also represses STAT3 signaling, limiting the initiation of NW mediated mammary[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"We identified that PRL activates STAT5, m-TOR and MEK and induces cell proliferation in FTE cells."

reach
"Insulin stimulates insulin response elements (IREs); prolactin induces STAT5 via the JAK-STAT pathway; hydrocortisone enhances the efficiency of milk protein gene expression by binding glucocorticoid [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"25 The ability of PRL to activate these pathways in vitro is inversely related to its ability to activate Stat5, 67 which also is reflected in PRL induced carcinomas in mouse models."

reach
"Fritsche et al. reported that WT p53 and p53 mutants retaining intact DNA-binding domain inhibited the transactivation potential of prolactin induced STAT5, as measured by STAT5 luciferase reporter as[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Stat5 could be activated by prolactin and its receptor, and by peptide growth factors and their receptors, e.g., HER4 has also been shown to activate Stat5."

reach
"In these cells Prl treatment strongly activates the STAT5, AKT, and MAPK signaling pathways and induces weak activation of the p65 NF-kappaB factor."

sparser
"To initiate milk production, mammary glands require activation of STAT5 by prolactin [ xref ]."

reach
"Our previous research showed that PRL treatment activated the Jak2 and STAT5 pathway in human mammary epithelial MCF-12A cells and that 5-HT treatment decreased beta-casein expression via the suppress[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"How oleic acid enhances prolactin induced STAT5 activation, while alone has no effect on STAT5 activation, is unclear."

sparser
"Next, the kinetics of JAK2-STAT5 activation by B2 or PRL was determined by western-blot analysis in CHO-PRLR cells, and representative results are shown in xref , respectively."

trips
"STAT5A-induced PRL in the conditioned medium can activate STAT5, STAT1, and to a lesser extent STAT3 in hCMEC/D3 cells, suggesting the existence of a positive feedback loop between STAT5 and PRL that promotes angiogenesis."

sparser
"STAT5 is predominantly activated by PRL, a pituitary hormone that plays a major role during the pre-lactogenic and lactation periods ( xref ; xref )."

reach
"Finally, the signaling cascade downstream of Prolactin and PRLR activated STAT3 rather than STAT5 in PDAC."

reach
"Interleukin-3, erythropoietin, and prolactin activate a STAT5 like factor in lymphoid cells."

reach
"Prolactin promotes STAT3 activation but not STAT5 :."

reach
"To further confirm this finding, we transfected Panc-1 cells with a 6xSTAT5-Luc reporter construct, and examined the prolactin induced STAT5 transcriptional activity."

sparser
"Acute injection of Prolactin (400 IU/kg) strongly induced activation of STAT5 in WT-NP mice and in CKO-NP mice (STAT5 activation after Prl treatment: WT Prl: 5,5-fold, CKO Prl: 4-fold vs. WT NaCl, ** P  < 0.01, n  = 6)."

sparser
"In addition, the time courses of JAK2 and STAT5 activation by PRL or B7 were also similar in CHO-PRLR cells."

sparser
"Direct injection of Prolactin activated STAT5 in both genotypes further explaining how sRlx via Prolactin and STAT5 activation could induce cardiomyocyte growth in both genotypes."

reach
"Prolactin increases the binding of Stat5 to the GAS motif of the Gck promoter and the Gck synthesis in beta-cells even in the absence of glucose XREF_BIBR, suggesting its action can be independent of glucose."

reach
"PRL increases expression and phosphorylation of ERalpha, and enhances alternative estrogen signaling, while estrogen induces transcription of both PRL and PRLR and potentiates PRL dependent STAT5 activity."

reach
"For example, prolactin and PDGF synergize Erk1/2 activation (but not STAT5 or Akt) in human breast cancer cells."

reach
"In this study we investigated the potential role of p100 in PRL induced Stat5 mediated transcriptional activation."

reach
"Others have shown that injection of supraphysiologic levels of prolactin caused STAT5 activation in all luminal cells, in contrast to the scattered pattern observed in the nonmanipulated state [XREF_BIBR, XREF_BIBR]."

sparser
"Prolactin (Prl) activation of STAT5 is necessary for casein gene expression."

sparser
"It is required for prolactin to activate Stat5, but it is not necessary for 3D cellular organisation."

reach
"While Prl activated Stat5 only in the epithelium, GH and EGF activated Stat5 preferentially in the stroma."

sparser
"Thus, it is possible that activated PRL receptor/JAK2 complex not only activates STAT5 by tyrosine phosphorylation but also transmits signals to the nuclear compartment that either lower the nuclear c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"We still have little knowledge about the role of PRL induced STAT5 activation in inflammatory responses; however, a recent report has involved the STAT5 activity in skin inflammation processes mediate[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"PRL-induced Stat5 activation is associated to high-grade prostate tumors and aggressiveness, and PRLR inhibition reduced tumor burden [ xref , xref ]."

reach
"Our findings demonstrate that GH, Prl, and EGF activate Stat5 in separate compartments, which in turn reflects their specific roles in ductal and alveolar development and differentiation."

reach
"PRL through PRLR can simultaneously activate the JAK and STAT5, PI3K-AKT, and PI3K-MAPK signaling pathways."

reach
"The antagonist used in the present study is known to block Prl induced STAT5 activation, and we observed that blocking PrlR reduced Prl induced activation of STAT3 and Erk in LAM cells."

reach
"To better identify this complex, we analysed the effect of PRL known to strongly activate Stat5 in mammary epithelial cells (Pierre et al., 1994)."

reach
"Growth hormone (GH) and prolactin, two hormones essential for normal development of pancreatic islet function and insulin secretion [XREF_BIBR, XREF_BIBR], require JAK2 as an essential signal transducer to activate STAT5 in the pancreas [XREF_BIBR]."

sparser
"The experiment shows that prolactin is able to activate STAT5 in SKBR3 cells in a dose-dependent manner."

reach
"It appeared that, in these cells, PRL was able to activate both Stat1 and Stat5 (Gouilleux et al., 1995; Stevens et al., 1995), but that only Stat1 binding was implicated in IRF-1 up-regulation (Wang [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"ERalpha and ERbeta were found to potently repress PRL induced STAT5 transcriptional activity on a beta-casein promoter construct in a ligand dependent manner."

reach
"In addition, Prl stimulated milk protein expression via phosphorylation of Stat5 was largely absent in primary mammary epithelial cells lacking beta1-integrin, indicating that it is essential for Prl induced activation of Stat5 [XREF_BIBR]."

reach
"In recent studies, we have demonstrated in breast cancer ERalpha + and HER2 + cells, up-regulation of PRLR transcription and expression induced by endogenous and exogenous PRL in the absence of estrogen via the long form of the prolactin receptor with essential participation of ERalpha and JAK2 and STAT5, mitogen activated protein kinase (MAPK) and PI3K pathways [XREF_BIBR]."

reach
"In compliant matrices, PRL activates STAT5 and stimulates development of well differentiated colonies."

sparser
"Similar C/EBPbeta, C/EBPdelta, STAT5, and Prl-activated STAT5 were found under all culture conditions."

reach
"PRL diminished lipid absorption by lowering lipoprotein lipase activity via STAT5 in human fat [54]."

reach
"Prolactin and oleic acid synergize STAT5 activation, but not Erk1/2 activation."

reach
"Further, PRL activated signal transducers and activators of transcription 1 (Stat1) and Stat5."

reach
"However, prolactin activated STAT5 in female postpartum suckling rat liver, resulting in transcriptional activation of Ntcp gene [20] ."

reach
"For example, prolactin activates STAT5 to control proliferation, differentiation and survival XREF_BIBR, while STAT3 is activated by IL-6 and LIF to control cell death during involution XREF_BIBR."

reach
"Taken overall, our findings demonstrate that GH and PRL activate Stat5 in separate compartments, which in turn reflects their specific role in ductal and alveolar development and differentiation (Gall[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"While cytokine i.e. GH and PRL-induced activation of STAT5 is mediated by the janus kinase (JAK)2, [3,20–22] , in insulin signalling, JAK2-dependent and independent STAT5 activation was reported [3,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Prolactin induced activation of STAT5 within the hypothalamic arcuate nucleus."

reach
"As an example, interleukin 6 and prolactin activate STAT3 and STAT5, respectively, to enhance the transcription of target genes in their target cell types [133, 134]."

sparser
"Accordingly, no activation of the transcription factor Stat5 by PRL can be detected in keratinocytes, Stat5 being nevertheless detected by Western blot."

sparser
"PRL-induced activation of the transcription factor STAT5 results in the up-regulation of numerous genes implicated in breast cancer pathogenesis."

sparser
"Both the SH2 domain and the kinase activity of JAK2 play a role in prolactin-dependent activation of JAK2 substrate STAT5."

sparser
"However, overexpression of CIS1 did not inhibit PRL-dependent STAT5 activation in 293 cells ( Fig. 2 ), while it partially inhibited EPO-dependent STAT5 activation [16] ."

reach
"Although the model predictions reproduce key aspects of the activation profile of STAT5 in INS-1 cells treated with prolactin, the model does not match experimental data for the 4-hour time point of pSTAT5A and the 4 and 6-h time points of pSTAT5B (Figs."

reach
"XREF_BIBR This suggests prolactin induced STAT5 activation and oleic acid induced activation of PPARdelta may increase cyclin D2 greater than either alone."

trips
"Activation of Stat5 by PRL in human breast cancer lines was associated with increased surface levels of the invasion-suppressive adhesion molecule E-cadherin in vitro and in xenotransplant tumors in vivo."

reach
"However, in contrast to the data available on insulin signaling, the relationship between the janus kinase 2 (JAK2)/STAT-5 pathway (canonically activated by prolactin and growth hormone) and the stimu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Our modeling predicts that SOCS negative regulation is not necessary for early activation, attenuation, and reactivation of STAT5 in pancreatic beta cells treated with prolactin."

sparser
"We have shown here that PRL-dependent STAT5 activation was weaker in ΔSH2 JAK2 clone with impaired centrosomal localization than in the JAK2 WT clone."

reach
"We also show that modulating upstream parameters such as the ligand binding rate and the initial value of receptor complexes can increase PRL mediated STAT5 activation."

reach
"Particularly in mammary epithelial cells, prolactin induces the association of STAT-5 with the p85-PI3K to activate AKT by means of a JAK2 dependent mechanism ( Sakamoto et al., 2007 )."

reach
"The lactogenic hormones (prolactin, insulin, cortisol) directly activate the JAK2–STAT5 signaling pathway [13,14], and activated STAT5 (pSTAT5) promotes milk synthesis [13]."

reach
"Activation of Stat5 by PRL in human breast cancer lines was associated with increased surface levels of the invasion-suppressive adhesion molecule E-cadherin in vitro and in xenotransplant tumors in vivo."

reach
"Prolactin induces a robust STAT5 activation in hypothalamic structures involved in the regulation of maternal behavior ( Brown et al., 2010; Furigo et al., 2014 ) such as the preoptic area ( Fig. 3 )."

sparser
"It has been shown that PRL-induced activation of MAPK/AP-1 pathway is inversely related to PRL-induced STAT5 activation [ xref – xref ]."

reach
"Alternatively, the hyperphagic behavior observed during lactation may be partially dependent on prolactin-induced STAT5 signaling in the brain."

sparser
"One example of a positive interaction is the synergistic activation of β-casein gene expression in the mammary gland, mediated by a direct physical interaction between prolactin-activated STAT5 and the GC receptor, which is activated by GCs [ xref ]."

reach
"Accordingly, we find that prolactin robustly activates STAT5 and MAPK signaling in rat and human myometrial cell lines."

reach
"Prolactin was described to stimulate the binding of STAT-5 to the Thp1 promoter in MIN6 cells and in isolated islets of mice ( Iida et al., 2015 )."

reach
"In addition, PRL has been reported to promote alveolar differentiation and milk production through Janus kinase 2–STAT5–Elf5 and receptor activator of nuclear factor κB ligand (RANKL) signaling [24]."

sparser
"3) that could potentially bind PRL-activated transcription factor Stat5 (signal transducer and activator of transcription 5) and the liganded androgen receptor (AR), respectively."

reach
"There were no statistically significant differences in DGAT , PERILIPIN2 and XDH by LPS or LTA treatment.The activation of STAT5 signaling stimulated by prolactin is indispensable for milk production [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In lactating BMECs, STAT5 activation stimulated by prolactin induces milk production, whereas STAT3 activation represses milk production in mastitis or after weaning [ 13 , 41 , 42 ]."

reach
"However, when cells were grown either on a nonadhesive substratum with LN1 or on top of 3D lrECM gels, Prl was able to bind to the exposed receptor and could activate STAT5 transiently."

reach
"In the mammary gland, Stat5 plays a key role in mammary epithelial cell growth and differentiation, and is activated in pregnancy by prolactin to promote terminal differentiation and milk production [[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"This study demonstrated that STAT5 can be activated by prolactin in mammary glands. xref Since then, several studies have further described the critical role of STAT5 proteins in adipogenesis, cellular differentiation, immune function, and oncogenesis. xref , xref STAT5 also controls cell survival through the regulation of prosurvival genes such as BCL-XL . xref In addition, STAT5 is activated by numerous cytokines such as IL-15, erythropoietin, growth hormone, and prolactin."

sparser
"Prolactin activates the Stat5 but not the Erk1/2 or Akt signaling pathways in medaka gill : The activation of cell signaling pathways was studied using dual labeling Western blots of lysates from meda[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"We report that (i) Stat5 is the major signaling cascade triggered by local PRL in the mouse dorsal prostate, (ii) this model recapitulates prostate tumorogenesis from precancer lesions to invasive carcinoma, and (iii) tumorogenesis involves dramatic accumulation and abnormal spreading of p63 positive basal cells, and of stem cell antigen-1-positive cells identified as a stem and progenitor like subpopulation."

sparser
"Thus, our data show that β1 integrin is critical for the Prl-induced activation of Stat5, a transcription factor essential for mammary epithelial differentiation, and they provide genetic evidence for cooperation between integrin and cytokine signaling pathways."

reach
"Regulation of MGF and Stat5 activity in cultured cells The mechanism of prolactin activation of MGF and Stat5 has been studied in COS cells co- transfected with cDNA encoding Stat5 and the prolactin r[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"A wide body of evidence points to a role of PRL-induced STAT5 activation in the progression of prostate cancer [148–150] ."

reach
"In response to prolactin, cSrc binds to the prolactin receptor (PrlR) and is required for the prolactin induced activation of Signal transducer and activator of transcription 5 (STAT5), a transcription factor downstream of PrlR regulating milk protein expression."

reach
"Prolactin treatment of the transfected cells caused activation of Stat5 within minutes."

reach
"GH or PRL alone strongly activates STAT5, STAT3 and AKT signaling in CHO-GHR or CHO-PRLR cells."

sparser
"STAT5 is mainly activated by the IL-2 cytokine family and IL-3 prolactin, but it can also be activated by the plate-derived growth factors EGF, EPO, GM-CSF, TPO, and GH."

reach
"IFA results found that H53 inhibits STAT5 nuclear transport induced by PRL."

reach
"Because human growth hormone (hGH) activates Stat1, 3, 5 and human prolactin (hPRL) activates Stat5, these results show that hPL uses a unique signal transduction pathway which is different from hGH and hPRL."

sparser
"Prolactin-induced activation of Stat5 was shown to be associated with a parallel increase in ncc2b expression."

sparser
"Second, β1 integrins are actively required for Prl signaling both in culture and in vivo because function-perturbing anti–β1 integrin antibodies block MEC differentiation ( xref ), a dominant-negative (DN) β1 integrin transgene compromises Stat5 activation and milk production ( xref ), and Prl cannot activate Stat5 in β1 integrin–null MECs ( xref )."

sparser
"Furthermore, an essential role for STAT5 activation by PRL has been reported in the induction of maternal behavior (for a detailed review, see Furigo et al., 2016 )."

sparser
"Although both forms of PRL activated both pathways to some extent, unmodified PRL predominantly activated Jak2-Stat5 and S179D PRL predominantly activated ERK 1/2 ( Wu et al., 2003 )."

sparser
"The data present here and in previous studies suggests that prolactin-induced STAT5 activation is necessary but not sufficient for alveolar formation but is necessary and sufficient for milk production."

sparser
"Not only has this work elegantly and conclusively shown that the PI3K/Akt pathway induces autocrine prolactin production which is required for the initiation of lactation, but it has the additional merit of the use of genetically altered mouse models to study the activation of STAT5 by prolactin in vivo in the correct cellular environment so we can be confident that the data are biologically relevant."

sparser
"One important advance was the discovery of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway; prolactin (PRL)-induced activation of JAK2 and STAT5 is required to induce expression of most, if not all, milk protein genes [ xref , xref ]."

sparser
"More recent evidence suggests early activation of STAT5 by PRL in the hypothalamic nuclei, within two minutes of IP PRL administration in male mice, indicating its direct and free transport to the bra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Expression of β-casein is synergistically regulated by prolactin-activated STAT5 and GC-activated GR ( Kabotyanski et al., 2006; Lechner et al., 1997; Stocklin et al., 1996; Stoecklin et al., 1999; Wy[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Our data indicate that in the mammary gland CIS and SOCS3 are involved in regulating STAT5 signaling at three different instances: 1) SOCS3 serves as a mediator of the inhibitory EGF effect on PRL-induced STAT5 activation; 2) CIS and SOCS3 play a role as negative feedback inhibitors of PRL action; 3) Inhibition of CIS and SOCS3 expression by glucocorticoids contributes to the positive effect of glucocorticoids on PRL-induced STAT5 activation."

reach
"To assess the signaling mechanism (s) involved in PRL mediated enhancement of hematopoiesis, we assayed the individual and combined effects of PRL and IL-3 on activation (i.e., tyrosine phosphorylatio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"To the best of our knowledge, this is the first observation of STAT-5 activation by PRL in nontransformed, human hematopoietic cells.Our studies show that PRL induces expression of CIS-1 and CIS-2, bu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Prolactin induced STAT5 activation resulted in an invasion-suppressive phenotype, including an increase in E-cadherin expression and reduced invasion through Matrigel."

reach
"It was reported that, in vitro, STAT5 could be activated directly by prolactin (PRL) without PRL mediated signal transduction."

sparser
"We still have little knowledge about the role of PRL-induced STAT5 activation in inflammatory responses; however, a recent report has involved the STAT5 activity in skin inflammation processes mediate[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Taken together, we conclude that TC-PTP is catalytically competent with respect to dephosphorylation and deactivation of PRL-activated STAT5 in the nucleus."

reach
"However, it has been shown in the HC11 mammary cell line that PRL activation of the STAT5 and MGF is insulin independent whereas expression of the beta-casein gene depends on the presence of insulin a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The transcriptional induction of a beta-casein promoter luciferase construct in transiently transfected COS cells is specific for the prolactin activation of MGF-Stat5; it is not observed in EPO- and GH-treated cells."

sparser
"The increased NTCP by prolactin (PRL)-activating Stat5 was repressed by further use of estradiol [ 71 ]."

reach
"This synergism could be mediated by the formation of a complex between PRL-activated STAT5 and the glucocorticoid receptor that stimulates milk-protein gene transcription, as has been reported by Stöc[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Stat5 is activated by prolactin, and its presence is mandatory for the proliferation and differentiation of mammary epithelium during pregnancy."

sparser
"We studied the mechanisms involved in the prolactin activation of Stat5 in COS cells co-transfected with cDNA encoding Stat5 and the prolactin receptor."

reach
"It is also possible that PRL induced Stat5 squelches limiting amounts of the coactivator CBP and p300 and thus antagonizes Stat1 mediated activation of the IRF-1 promoter [20]."

sparser
"By examining the ability of pre-expression of ΔS2SF1b to affect acute (15 min) PRL activation of Stat5 at the LF, and chronic (48 h) PRL activation of a response element with multiple Stat5 binding si[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"To investigate the influence of prolactin induction of Stat5 on p53 transcriptional activity COS7 cells were transfected with the prolactin receptor, Stat5 and the PG13-luciferase construct, a reporte[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In the developing breast, STAT5 is activated by prolactin (mainly) and other signaling pathways, such as hormonal receptors and EGFR, and promotes its’ terminal differentiation and lactation [26] ."

sparser
"STAT5 is activated by prolactin and is essential for both mammary development and milk production."

reach
"Despite evidence for signaling crosstalk, it was unclear how the PRL and its receptor might activate the PI3K and AKT pathway in a JAK2- or STAT5 dependent manner in the mammary epithelium."

sparser
"Instead, we demonstrate that prolactin activation of Stat5 results in the formation of a complex between phospho-Stat5 and BRCA1 that inhibits the function of BRCA1 at the p21 promoter."

reach
"Activation of Stat5 by prolactin in COS7 cells has no influence on the transactivation of p53 dependent reporter construct by p53."

sparser
"Consistent with previous results, prolactin activated Stat5 whereas S179DPRL did not ( Fig. 7 , showing examples of T47D and PC3 cells with endogenous high and low expression of PRLRs, respectively)."

reach
"In many tissues expressing Stat5, this protein can be activated by GH and PRL as well as several cytokines including EPO ( Toukine et al., 1995; Ram et al., 1996 )."

sparser
"Others have shown that integrin-linked kinase (ILK) couples β1 integrin to Rac1, promoting PRL-induced STAT5 activation and, eventually, β-casein gene expression ( xref )."

reach
"Furthermore, an essential role for STAT5 activation by PRL has been reported in the induction of maternal behavior (for a detailed review, see Furigo et al., 2016 )."

sparser
"We conclude that prolactin and other hormones/cytokines that activate Stat5 can have a major impact on tumor development by interfering with the cell cycle regulatory function of wild type BRCA1."

reach
"It has been determined that PRL treatment induces up-regulation of the JAK2/STAT5 pathway in the medial preoptic area (mPOA), PVN, supraoptic nucleus (SON), and the ARC of the hypothalamus, areas requ[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"More recent evidence suggests early activation of STAT5 by PRL in the hypothalamic nuclei, within two minutes of IP PRL administration in male mice, indicating its direct and free transport to the bra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Additionally, CyPB potentiates prolactin induced STAT5 transactivation by promoting the dissociation of PIAS3, a STAT5 repressor."

reach
"PRL induced tumors display inverse Stat5 and AP-1 activation and elevated epithelial pAKT."

sparser
"Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects."

reach
"The increased PRL and PRLR combination could activate the kinase 2 (JAK2) and transcription 5 (STAT5) signaling pathways (Figure 6)."

reach
"Its involvement in tumorigenesis is linked to prolactin receptors (PRLrs), which can activate the transcription factor STAT5 [5]."

sparser
"As an example, interleukin 6 (IL-6) and prolactin (PRL) generally activate STAT3 and STAT5, respectively, in relevant cell types to up-regulate transcription of target genes ( DaSilva et al., 1996; Hi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Therefore, STAT5 activation by PRL is indispensable for initiating β-casein expression."

sparser
"It was reported that, in vitro, STAT5 could be activated directly by prolactin (PRL) without PRL-mediated signal transduction."

reach
"These authors proposed that in the peripartum the mammary gland is protected against deleterious actions of TH such as inducing premature involution ( Varas et al., 2002 ) or blocking PRL-induced STAT[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"In contrast to the role of NOTCH, activation of Janus kinase 2 (JAK2) and STAT5 by prolactin leads to alveolar differentiation and β-casein production xref ."

reach
"To determine whether Src was required for PRL induced activation of STAT5 and expression of beta-casein we utilized primary mammary epithelial cells (MECs) isolated from the mammary glands of Src -/-, Src +/-, and Src +/+ mice."

reach
"Previous studies have also demonstrated that prolactin stimulated Stat5 activates the human HSD3B2 promoter XREF_BIBR."

reach
"In addition to its pivotal role for mammary epithelial cell proliferation, specification, and differentiation, we demonstrate that this kinase is indispensable for the prolactin mediated activation of Stat5 and the maintenance of functionally differentiated alveolar cells during lactation."
| PMC

reach
"There is a hypothesis that the accumulation of nuclear factor (NF)-I isoforms coupled with Prl-mediated activation of STAT5 during mammary gland development is crucial for the appropriate temporal and[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"RU 486 was not able to cause an increase in transcription of the β-casein promoter construct over that observed with prolactin activated Stat5 alone."

reach
"Reporter assays using HeLa cells transfected with the beta-casein promoter-luciferase construct and ectopically expressing STAT5 and p300 showed that p300 increased prolactin induced STAT5 transcriptional activity [XREF_BIBR]."

reach
"In addition, the time courses of JAK2 and STAT5 activation by PRL or B7 were also similar in CHO-PRLR cells."

reach
"Finally, loss of SOCS-1 expression in SOCS-1 (-/-) mouse embryonic fibroblast (MEF) cells led to attenuation in SHP-1 function to down-regulate PRL induced Stat5 activation."

sparser
"It appeared that, in these cells, PRL was able to activate both Stat1 and Stat5 ( Gouilleux et al., 1995; Stevens et al., 1995 ), but that only Stat1 binding was implicated in IRF-1 up-regulation ( Wa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"XREF_BIBR PRL induces STAT5 activation via JAK2 and also functions in suppressing the invasive capacity of breast cancer cells."