IndraLab
Statements
sparser
"Mechanistic studies revealed that upon hypoxia‐induced activation, JAK2 phosphorylates STAT3, which then translocates into the nucleus, where it binds to the CCNA2 promoter to transcribe cyclin A2 expression, thereby promoting PASMC hyperplasia along with pulmonary vascular remodelling (Figure xref )."
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"Stat3 is frequently phosphorylated and activated in the majority of breast and ovarian cancers [XREF_BIBR], where cytokines and growth factors such as IL-6 bind to specific receptors and activate JAK2 which, in turn, phosphorylates Stat3 and prompts translocation of pStat3 to the nucleus."
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"On the other hand, in mammals, it has been reported that hepcidin can also act as an anti-inflammatory agent inducing a signal cascade by hepcidin activated Jak2, which phosphorylates the transcription factor Stat3, subsequently provoking an anti-inflammatory transcriptional response by negative feedback."
rlimsp
"Through the first cascade, nicotine stimulation of α7 nAChR directly activates JAK2, which in turn could phosphorylate both PI3K and STAT3, as has already been demonstrated conclusively in previous studies [16], [52] and is also supported by our results in MØ (Figure 3D); both activated signals would eventually, and independently, results in increased IRAK-M expression."
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"GH induced JAK2 phosphorylation was greater in knockout (KO) than in wild-type (WT) PTP-1B embryonic fibroblasts and resulted in increased tyrosine phosphorylation of STAT3 and STAT5, while overexpression of PTP-1B reduced the GH mediated activation of the acid-labile subunit gene."
sparser
"To ensure that the in vitro phosphorylation of stat3 by PKM2 and the R399E was at comparable physiological conditions, we compared the phosphorylation of the GST-stat3 by JAK2 and R399E. Clearly, very similar levels of stat3 phosphorylations were observed by both kinases ( xref )."
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"Through the first cascade, nicotine stimulation of alpha7 nAChR directly activates JAK2, which in turn could phosphorylate both PI3K and STAT3, as has already been demonstrated conclusively in previous studies XREF_BIBR, XREF_BIBR and is also supported by our results in MO (XREF_FIG); both activated signals would eventually, and independently, results in increased IRAK-M expression."
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"These findings indicated that JAK2 inhibition by Rux in MCAO mice decreased the phosphorylation of STAT3, thus inhibiting downstream proinflammatory cytokines and acetylation of H3 and H4 on the NLRP3 promoter, resulting in a limitation of NLRP3 inflammasome activation.Rux, a selective oral JAK 1/2 inhibitor, is mainly used to treat polycythemia vera (6) and recalcitrant dermatomyositis (7), as well as myelofibrosis (8), due to its antitumor (9), immunosuppressive and anti-inflammatory functions (10)."
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"Then the complex binds to the receptor subunit homodimer gp130 of IL-6, resulting in selective activation of JAK1, JAK2, and TYK2, which in turn promotes the recruitment and phosphorylation of STAT1, STAT3, and to a lesser extent STAT5.52–54 Ishizaki et al found various inflammatory cytokines, such as IL-6, IL-1b, and matrix metalloproteinases (MMPs), such as MMP3 and MMP9, were significantly reduced in Tyk2−/− mice.55
JAK Inhibitors Progress."
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"As shown in XREF_SUPPLEMENTARY, we found that the JAK2 and STAT3 double inhibitor WP1066 is able to inhibit STAT3 phosphorylation and reverse miR-204 induction upon vemurafenib treatment, while the JAK2 single inhibitor AZD1480 (XREF_SUPPLEMENTARY), the SRC inhibitor PP1 and the PI3K inhibitor wortmannin are not (XREF_SUPPLEMENTARY)."
sparser
"As JAK2-phosphorylated STAT3 is the key pathway in IL-6 effects, and RIG-I deficiency failed to promote IL-6-STAT3 activation under inhibition of JAK2 (Additional file xref : Fig. S3e), hepatic RIG-I deficiency-promoted STAT3 activation is mediated by the enhanced JAK2-STAT3 interaction."
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"Moreover, the PI3K inhibitor wortmannin blocked activation of STAT3 and Akt without affecting the JAK2 activation, whereas JAK2 inhibitor AG490 suppressed the levels of phospho-STAT3, phospho-Akt, and PI3K, suggesting that PI3K activation occurs after JAK2 phosphorylation, and both PI3K and JAK2 kinases cooperate to mediate STAT3 and Akt phosphorylation."
sparser
"The finding that JAK2, STAT3 and PI3K contribute equally to nicotine-induced IRAK-M overexpression ( xref ) suggests that these three signaling molecules may be chained or converge in a common signaling pathway leading to the induction of IRAK-M. To test this hypothesis we focused our attention on those signaling routes that, according to previous studies (for more detail, see references in the corresponding section of Discussion), provide connection for the above signaling molecules: activated JAK2 can phosphorylate either STAT3 or PI3K/Akt and activated PI3K can phosphorylate STAT3."
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"The activated JAK2 recruits and phosphorylates STAT3 for its activation and translocation to the arcuate nucleus in the hypothalamus, which regulates the expression and neuronal excitability of POMC, AgRP, and NPY, ultimately suppressing appetite, promoting energy expenditure, and reducing body weight [XREF_BIBR]."
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"We show that oncogenic JAK2 (Janus kinase 2) activity caused STAT3 (signal transducer and activator of transcription 3) and STAT5 phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein expression in JAK2 V617F -mutant cells, whereas blockade of JAK2 reduced PD-L1 expression in myeloid JAK2 V617F -mutant cells."
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"Among the seven members of the STAT family, STAT3, particularly phosphorylated by JAK2, is one of the major players that has been detected in many cancers, including the brain, breast, ovarian, pancreatic, prostate, melanoma, squamous cell carcinoma [XREF_BIBR], and lung [XREF_BIBR]."
| PMC
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"These data indicated that this compound did not inhibit the phosphorylation of upstream kinases but inhibited STAT phosphorylation, most likely by inhibiting the association of STAT with JAK or cytokine receptors; however, this compound could not inhibit STAT3 phosphorylation by JAK2 and Lyn in vitro , suggesting that another cellular protein was required for this compound to inhibit STAT phosphorylation."
sparser
"Recent studies have shown that JAK2 phosphorylated signal transducer and activator of transcription 3 (STAT3) bound to CCNA2 promoter to boost cyclin A2 production, thereby promoting PASMC proliferation and resulting in PAH. xref Meanwhile, miR‐508‐3p mimics inhibited ovarian cancer cell proliferation, migration by directly targeting the 3′‐UTR of CCNA2. xref Therefore, whether miR‐508‐3p could mediate CCNA2 to alleviate PAH required more investigation."
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"CONCLUSION: JAK2 inhibition by Rux in MCAO mice decreased STAT3 phosphorylation, thus inhibiting the expression of downstream proinflammatory cytokines and the acetylation of histones H3 and H4 on the NLRP3 promoter, resulting in the downregulation of NLRP3 inflammasome expression."
sparser
"Subsequently, JAK2 kinase triggered the phosphorylation of STAT3 protein, followed by separation of phosphorylated STAT3 from the IL-22 receptor, which combined with each other between the 608 Arg and the phosphorylated Tyr 705 to form a dimer in cytoplasm finally migrated to the nucleus xref ."
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"While the most straightforward conclusion of these results is that parasite triggered JAK2 activation mediates STAT3 phosphorylation, this interpretation must be treated with caution in light of recent evidence that ROP16 directly acts on STAT molecules in a manner sensitive to JAK chemical inhibition XREF_BIBR."
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"Binding of IL-6 family cytokines to their cognate receptors, all of which comprise a common gp130 subunit, causes the activation of Janus tyrosine kinase (JAK)-1 and JAK2 which in turn tyrosine phosphorylate signal transducer and activator of transcription (STAT)-1 and STAT3 (20, 21)."
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"Another feasible rationale is to target downstream effectors of PBX1 such as JAK2 and STAT3 (JAK2, a tyrosine kinase that directly phosphorylates and activates STAT3) that leads to transcriptional activation of various STAT3 regulated genes that work in concert to promote tumor progression [XREF_BIBR]."
rlimsp
"To test this hypothesis we focused our attention on those signaling routes that, according to previous studies (for more detail, see references in the corresponding section of Discussion), provide connection for the above signaling molecules: activated JAK2 can phosphorylate either STAT3 or PI3K/Akt and activated PI3K can phosphorylate STAT3."
sparser
"We found that EGFR signaling was blocked by a small molecule (G5-7) that selectively inhibited Janus kinase 2 (JAK2)–mediated phosphorylation and activation of EGFR and STAT3 (signal transducer and activator of transcription 3) by binding to JAK2, thereby decreasing the activity of downstream signaling by mTOR (mammalian target of rapamycin) and inducing cell cycle arrest."
sparser
"IL6 binding to the IL6 receptor is classically followed by the activation of receptor-bound JAK1 and JAK2 kinases, which in turn phosphorylate the signal transducer and activator of transcription 3 (STAT3) that is then translocated as a dimer to the nucleus where it activates the transcription of IL6 sensitive genes xref ."
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"Activated JAK2 auto-phosphorylates its receptors, and additionally phosphorylates STAT3, which results in the dimerization and translocation of STAT3 into the nucleus, where it binds to specific regulatory sequences to activate or repress transcription of target genes [XREF_BIBR]."
sparser
"Besides the indirect stimulatory role of leptin on the synthesis of TRH through a-MSH released by POMC neurons and stimulating pCREB (in 66% of Trh-expressing cells in mid PVN), it has direct stimulatory effects on TRHergic neurons activating its receptor Lep-Rb inducing the phosphorylation of Janus kinase 2 that in turn phosphorylates signal transducer and activator of transcription 3 (in 28% of cells) allowing its binding to Trh promoter (104, 109, 110)."
sparser
"The upstream effect of ROS on STAT3 activation not only involves the activation of Jak2 (Janus kinase 2) and TYK2 (tyrosine kinase 2) that phosphorylate STAT3 [ xref ], but also oxidation-mediated inhibition of the low molecular weight protein tyrosine phosphatase (LMW-PTP) that dephosphorylates Jak2 [ xref ]."
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"190 In the development of the central nervous system, Hes proteins, downstream effectors of Notch, directly bind to STAT3 and induce phosphorylation by recruiting JAK2, indicating that Hes proteins may be non-receptor scaffold proteins that facilitate JAK2 phosphorylation of STAT3."
sparser
"IL-23, through binding to its receptor IL-23R, promotes the phosphorylation of the signal transducer and activator of transcription 3 (STAT3) by janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2), allowing its entrance into the nucleus and enhancing the expression of the retinoic acid receptor-related orphan receptor gamma t (RORγt), which is responsible for the expression of IL-17 and other Th17 cytokines [ xref , xref ]."
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"Mechanistic studies revealed that upon hypoxia‐induced activation, JAK2 phosphorylates STAT3, which then translocates into the nucleus, where it binds to the CCNA2 promoter to transcribe cyclin A2 expression, thereby promoting PASMC hyperplasia along with pulmonary vascular remodelling (Figure 7)."
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"IL6 binding to the IL6 receptor is classically followed by the activation of receptor-bound JAK1 and JAK2 kinases, which in turn phosphorylate the signal transducer and activator of transcription 3 (STAT3) that is then translocated as a dimer to the nucleus where it activates the transcription of IL6 sensitive genes ."
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"Insulin signals through a receptor tyrosine kinase that phosphorylates and activates the docking proteins IRSs (insulin receptor substrates), whereas the leptin receptor and its associated protein tyrosine kinase JAK2 (Janus kinase 2) mediate phosphorylation and activation of the transcription factor STAT3 (signal transducer and activator of transcription)."
sparser
"190 In the development of the central nervous system, Hes proteins, downstream effectors of Notch, directly bind to STAT3 and induce phosphorylation by recruiting JAK2, indicating that Hes proteins may be non-receptor scaffold proteins that facilitate JAK2 phosphorylation of STAT3.191 In breast cancer, the Notch signaling pathway is often hyperactivated, noncanonical Notch signaling upregulates IL-6 expression, then activates downstream JAK/STAT, and Notch-mediated IL-6 upregulation occurs only when p53 was mutated or lost."
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"After knocking down the FEZF1-AS1 of KYSE150 and KYSE510 cells by the constructed lentiviral expression vector, the changes of cell cycle were detected by flow cytometry, the ability of cell proliferation by colony formation assay, the ability of cell invasion by Transwell TM invasion assay, the ability of cell migration by Transwell TM migration and scratch assay, and the protein levels of JAK2 and phosphorylated STAT3 (p-STAT3) by Western blotting."
sparser
"Furthermore, JAK2 V617F, a constitutively active JAK2 mutant, phosphorylates both STAT3 and STAT5 proteins and has high frequency in patients with hematopoietic stem cell diseases, such as myeloproliferative diseases, essential thrombocythemia, polycythemia vera (PV), and idiopathic myelofibrosis (IMF) [ xref ]."
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"JAK2 phosphorylates STAT3 to transduce VEGF/VEGFR-2 signaling and promote vascular permeability. (A)
STAT3 transcriptionally activates ICAM1, a cell adhesion molecule that promotes vascular permeability. (A) The pGL3-ICAM1-WT plasmid (top) containing the human ICAM1 promoter with a STAT3 binding site located at -115 to -107bp."
sparser
"Leptin signaling begins with the phosphorylation of janus kinase 2 (JAK2), which in turn phosphorylates signal transducer and activator of transcription 3 (STAT3), leading to its translocation to the nucleus, where it activates Pomc transcription and inhibits Npy and Agrp transcription [ xref , xref , xref , xref ]."
| PMC
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"Curcumin ( xref ) is known to inhibit STAT3 phosphorylation by EGFR, Src, and Jak2, the upstream kinases responsible for activation of STAT3 whereas AG490 ( xref ) is a specific inhibitor of Jak2 kinase which is primarily responsible for STAT3 phosphorylation through IL-6 receptor."
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"These data indicated that this compound did not inhibit the phosphorylation of upstream kinases but inhibited STAT phosphorylation, most likely by inhibiting the association of STAT with JAK or cytokine receptors; however, this compound could not inhibit STAT3 phosphorylation by JAK2 and Lyn in vitro, suggesting that another cellular protein was required for this compound to inhibit STAT phosphorylation."
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"Our analysis revealed that binding motifs of STAT1, STAT3 and STAT5, which are phosphorylated by JAK2, specifically associate with the observed LPS-specific hypomethylated CpGs and expression changes.JAK/STAT signaling is not directly downstream of TLR4/TLR2 receptors, and its activation requires the production of other molecules, such as IFNγ or IL-6, in order to activate the pathways autocrinally or paracrinally through their receptors (6, 47)."
sparser
"190 In the development of the central nervous system, Hes proteins, downstream effectors of Notch, directly bind to STAT3 and induce phosphorylation by recruiting JAK2, indicating that Hes proteins may be non-receptor scaffold proteins that facilitate JAK2 phosphorylation of STAT3."
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"Molecular docking studies showed that ASI had the potential to interact favorably with target genes involved in the JAK/STAT signaling pathway, such as JAK2 and STAT3.The experimental results showed that ASI could significantly alleviate Chlorhexidine Gluconate (CG)-induced peritoneal histopathological changes and increase JAK2 and STAT3 phosphorylation levels."
sparser
"The activated JAK2 recruits and phosphorylates STAT3 for its activation and translocation to the arcuate nucleus in the hypothalamus, which regulates the expression and neuronal excitability of POMC, AgRP, and NPY, ultimately suppressing appetite, promoting energy expenditure, and reducing body weight [ xref ]."
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"IL27 signal through their interaction with IL27 receptor [IL27R (IL27Rα/ Gp130)] on the cell surface, triggering the activation of JAK1/ JAK2, which phosphorylates and activates STAT1/STAT3 transcription factors (Pflanz et al., 2004; Huber et al., 2007; Pradhan et al., 2007; Kwock et al., 2020) ."
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"Upon inhibition of the phosphorylation of JAK2/STAT3 by the JAK2/STAT3 inhibitor AG490, the up-regulated expression and translocation of HMGB1 was reduced and EBI was ameliorated, further highlighting the contribution of JAK2/STAT3 pathway in HMGB1-mediated neuroinflammation in SAH [76]."
sparser
"Activated Jak2 phosphorylates STAT3 and SOCS3 transcription factors which bind to DNA and transactivates an anti-inflammatory gene response ( xref ), decreases the nuclear translocation of the proinflammatory cytokine transcription factor NF-κB ( xref , xref ), and reduces the transcription of the high mobility group box 1 (HMGB1) DNA-binding protein ( xref ) ( xref , adapted from Sternberg; 277)."