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PTK6 activates STAT3. 61 / 64
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"The murine homolog of the human breast tumor kinase (BRK) substrate (BKS), also known as Signal transducing adaptor protein-2 (STAP-2), was seen to be a further critical STAT3-interacting protein playing an important role in BRK-dependent STAT3 activation [ xref ]."
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"Although characterization of PTK6 in the normal gastrointestinal tract suggested that it might function as a tumor suppressor, recent in vivo studies demonstrated that disruption of Ptk6 impairs STAT3 activation and subsequent tumorigenesis following carcinogen administration."
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"In addition, we identified several IL pathways signaling (IL-6, −35, −9, −21, −4, and −13), PTK6 activates STAT3, antigen presentation: folding, assembly, and peptide loading of MHC class I, and endoplasmic reticulum (ER)-phagosome pathway in the CD4 + T IFN + cluster; IFN α/β signaling in the CD4 + T naive cluster; and IL-35 signaling and ER-phagosome pathway in the CD4 + T act1 cluster, which are among the top overrepresented pathways found in the Mtb- infected lungs compared to uninfected lungs."
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"These results suggest that while Brk mediated STAT3 phosphorylation may be relevant to the growth of established mammary tumors, forced expression of Brk does not appear to drive phospho-STAT3 during the initiation of involution."
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"Importantly, recent studies have shown that STAT3 is a Brk substrate and that Brk activates STAT3 [17] ."
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"To further verify the role of endogenous Cbl in Brk/STAP-2-mediated STAT3 activation, we tested the effect of Cbl siRNA on Brk-induced STAT3-LUC activation in HeLa/STAP-2 transformants."
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"Inhibitory phosphorylation of PTK6-WT prevents activation of STAT3 and ERK5 in cells overexpressing PTK6-WT (XREF_FIG)."
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"PTK6 phosphorylates and activates STAT3 in cell lines ( xref ) and increased STAT3 activation was observed in Ptk6 +/+ mice, compared with Ptk6 −/− mice, after AOM administration ( xref )."
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"Similar to Ack1, Brk activates STAT3 and STAT5 through phosphorylation, thereby enhancing the transcriptional activity of STATs."
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"PTK6 activates STAT3 [XREF_BIBR] and STAT5b [XREF_BIBR] to promote proliferation, and this may be facilitated by the signal transducing adaptor protein-2 (STAP2) [XREF_BIBR]."
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"Active ectopic PTK6 promotes STAT3 activation in normal mammary gland and mammary gland tumors."
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"As shown in Fig. 3 A, STAP-2 WT markedly up-regulated Brk mediated STAT3 activation."
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"Furthermore, we demonstrate that a reduction of endogenous STAP-2 expression decreases Brk mediated STAT3 activation.Reagents and antibodies."
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"Furthermore, STAP-2 Tryr-250 phosphorylation was found to be important for Brk induced STAT3 transcriptional activation [XREF_BIBR]."
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"Disruption of Ptk6 reduced activity of STAT3 in young adult mouse colon cells."
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"To confirm the effect of STAP-2 Y250F on Brk mediated STAT3 activation, we transfected 293T cells with STAP-2 WT or STAP-2 Y250F together with Brk and STAT3-LUC."
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"In addition, small interfering RNA mediated reduction of endogenous STAP-2 expression strongly decreased Brk mediated STAT3 activation in T47D breast cancer cells."
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"PTK6 phosphorylates and activates STAT3 in cell lines and increased STAT3 activation was observed in Ptk6 +/+ mice, compared with Ptk6 -/- mice, after AOM administration."
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"Silencing PTK6 reduced ERK1/2 activation, but not AKT or STAT3 activation, while PTK6 overexpression increased ERK1/2 activation."
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"PTK6 activates STAT3 [ xref ] and STAT5b [ xref ] to promote proliferation, and this may be facilitated by the signal transducing adaptor protein-2 (STAP2) [ xref ]."
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"Brk is constitutively activated in transformed T and B cells, despite not being expressed in normal, unstimulated lymphocytes. xref In colorectal cancer cells, Brk phosphorylates JAK2 to activate JAK2/STAT3 signaling, contributes to cell stemness, and confers resistance to chemotherapy. xref Similar to Ack1, Brk activates STAT3 and STAT5 through phosphorylation, thereby enhancing the transcriptional activity of STATs. xref However, the current knowledge of the roles of both Ack1 and Brk in immune cells is limited."
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"Importantly, small interfering RNA mediated reduction of endogenous STAP-2 expression decreased Brk mediated STAT3 activation."
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"In the present study, manipulated STAP-2 expression demonstrated essential roles of STAP-2 in Brk mediated STAT3 activation."
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"Taken together, our findings demonstrate that STAP-2 is phosphorylated at Tyr250 by Brk, and plays an important role in Brk mediated STAT3 activation."
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"By contrast, the STAP-2 Y250F transfectant failed to show enhanced Brk mediated STAT3 activation, while protein expression levels of STAP-2 WT and STAP-2 Y250F were similar."
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"Disruption of Ptk6 impairs STAT3 activation."
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"STAT3 activation has been linked to colon tumorigenesis XREF_BIBR, XREF_BIBR, and PTK6 was shown to phosphorylate and activate STAT3 in cell lines 20."
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"Furthermore, Brk expression enhanced STAT3 dependent transcription."
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"In addition, we identified several IL pathways signaling (IL-6, −35, −9, −21, −4, and −13), PTK6 activates STAT3, antigen presentation: folding, assembly, and peptide loading of MHC class I, and endoplasmic reticulum (ER)-phagosome pathway in the CD4 T IFN cluster; IFN α/β signaling in the CD4 T naive cluster; and IL-35 signaling and ER-phagosome pathway in the CD4 T act1 cluster, which are among the top overrepresented pathways found in the Mtb-infected lungs compared to uninfected lungs."
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"Thus, although Pyk2, Vav1, and STAP-2 bind to each other, their binding seems to be independent.In our previous study, we showed that STAP-2 Y250 is a major site for phosphorylation by Brk and critica[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In an AOM and DSS (azoxymethane and dextran sodium sulfate) murine colon cancer model, disruption of Ptk6 prevents activation of STAT3 and decreases AOM induced colon tumorigenesis in mice."
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"To further assess the functional relevance of STAP-2 in Brk mediated STAT3 activation, we examined whether siRNA mediated reduction of endogenous STAP-2 affects Brk mediated STAT3 activation."
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"Furthermore, overexpression of the STAP-2 Y250F mutant protein affected Brk mediated STAT3 activation."
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"PTK6 promotes STAT3 activation in the colon following injection of the carcinogen azoxymethane and regulates STAT3 activity in mouse colon tumors and in the HCT116 and young adult mouse colon cell lines."
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"Importantly, recent studies have shown that STAT3 is a Brk substrate and that Brk activates STAT3 [17]."
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"Additionally, unidentified phosphorylation sites involved in Brk mediated STAT3 activation may exist in the PH domain of STAP-2."
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"Targeting PTK6 impairs STAT3 activation following DNA damage."
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"In contrast, overexpression of constitutively active PTK6 promoted STAT3 and ERK5 activation in colon cancer cells, and endogenous PTK6 promoted cell survival and oncogenic signaling in response to DNA damaging treatments."
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"To further verify the role of endogenous Cbl in Brk and STAP-2-mediated STAT3 activation, we tested the effect of Cbl siRNA on Brk induced STAT3-LUC activation in HeLa and STAP -2 transformants."
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"Disruption of Ptk6 impairs activation of STAT3 in vivo and in vitro."
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"STAP-2 is phosphorylated at tyrosine 250 by Brk and modulates Brk mediated STAT3 activation."
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"PTK6 activates signal transducer and activator of transcription 3 (STAT3), and active STAT3 was detected in PTK6-positive mammary gland epithelial cells."
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"Lack of PTK6 mediated activation of STAT3 could at least in part explain our finding that disruption of PTK6 impairs UVB induced tumorigenesis in the mouse."
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"Liu et al. reported that Brk is able to induce transcriptional activation of STAT3 leading to a cooperative increase in cell proliferation [XREF_BIBR]."
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"Importantly, a reduction of STAP-2 expression in HeLa cells decreased Brk mediated STAT3-LUC activation, indicating that endogenous STAP-2 is involved in the regulation of Brk mediated STAT3-LUC activ[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"It was also observed that the attenuation of BRK phosphorylation in turn inhibits BRK mediated activation of its direct targets, STAT3, SAM68, and Paxillin."
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"In HeLa and STAP -2 cells, Brk expression induced STAT3 activation in a dose dependent manner."
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"siRNA-mediated reduction of endogenous Cbl expression resulted in a significant enhancement of Brk-induced STAT3-LUC activation in these cells ( Fig. 3 D, upper panel)."
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"PTK6 promotes CRC progression by activating JAK2/STAT3 signaling."
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"In the present study, we focused on the involvement of STAP-2 Tyr250 in Brk mediated STAT3 activation, because STAP-2 Tyr250 is the major site of phosphorylation by Brk, as shown in Fig. 1."
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"PTK6 promotes STAT3 activation in the colon following injection of the carcinogen azoxymethane and regulates STAT3 activity in mouse colon tumors and in the HCT116 and YAMC cell lines."
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"STAT3 has been shown to promote tumor initiation of different tumor types, including those of the gastrointestinal tract and skin, and PTK6 was previously shown to promote STAT3 activation and tumorigenesis in mouse models of colon and skin cancer."
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"Here, we also confirmed a stimulatory role of IL-6 on the phosphorylated activation of PTK6, which subsequently enhanced the stemness and chemoresistance of CRC through activating the JAK2/STAT3 signaling."
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"One of STAT3 target gene products is the suppressor of cytokine signaling 3 (SOCS3), which was recently shown to inhibit BRK induced activation of STAT3 XREF_BIBR."
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"Taken together, these results suggest that phosphorylation of Y250 in STAP-2 affects but is not required for Brk mediated STAT3 activation."
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"Knockdown of STAP-2 disrupts PTK6 activation of STAT3 and STAT5 [ xref , xref , xref ]."
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"PTK6 activates signal transducer and activator of transcription 3 (STAT3), and active STAT3 was detected in PTK6 positive mammary gland epithelial cells."
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"As shown in Fig. 2 B, STAP-2 WT, but not Y250F, positively stimulated Brk mediated STAT3 activation, while protein expression levels of STAP-2 WT and STAP-2 Y250F were similar."
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"Although PTK6 regulates growth suppression and differentiation in the normal intestine, our data indicate that PTK6 is able to promote STAT3 activation and development of colorectal cancers in vivo."
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"Disruption of Ptk6 reduced activity of STAT3 in YAMC cells."
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"miR-214 negatively regulated PTK6 expression to impair the JAK2 and STAT3 pathway activation, thereby halting CC cell proliferation, migration, invasion, xenograft tumor growth and metastasis."
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