Source:http://linkedlifedata.com/resource/pubmed/id/14963038
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
17
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| pubmed:dateCreated |
2004-4-19
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| pubmed:abstractText |
Signal transducers and activators of transcription factors (STATs) mediate many of the cellular responses that occur following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine and serine phosphorylation, which normally occurs as a tightly regulated process. Dysregulated STAT activity may facilitate oncogenesis, as constitutively activated STATs have been found in many human tumors as well as in v-abl- and v-src-transformed cell lines. Pyk2 is a member of the focal adhesion kinase family and can be activated by c-Src, epidermal growth factor receptor (EGFR), Janus kinase 1, tyrosine kinases, and G-protein-coupled receptor signaling. Although Pyk2 has been implicated in Janus kinase-dependent activation of MAPK and Stat1, no role for Pyk2 in the activation of other STAT proteins has been ascribed. Here, we provide evidence that Pyk2, along with c-Src, facilitates EGFR-mediated Stat3 activation. Pyk2 expression in HeLa cells induces Stat3 reporter gene activation and Stat3 phosphorylation on amino acid residues Tyr-705 and Ser-727. Together Pyk2 and c-Src potently activate Stat3, and Pyk2 enhances Stat3-induced cell proliferation. Moreover, the expression of a dominant negative version of Pyk2 impairs c-Src-induced Stat3 activation and cell proliferation. The treatment of A431 cells with EGF results in the recruitment of c-Src, Pyk2, and Stat3 to the EGFR and the phosphorylation of c-Src, Pyk2, and Stat3. Expression of constructs for dominant negative forms of either Pyk2 or c-Src impair EGF-induced Stat3 phosphorylation. These results indicate that Pyk2 facilitates EGFR- and c-Src-mediated Stat3 activation, thereby implicating Pyk2 activation as a potential co-mediator in triggering Stat3-induced oncogenesis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CSK tyrosine-protein kinase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
23
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| pubmed:volume |
279
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
17224-31
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| pubmed:dateRevised |
2011-11-2
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| pubmed:meshHeading |
pubmed-meshheading:14963038-Cell Division,
pubmed-meshheading:14963038-Cell Line, Transformed,
pubmed-meshheading:14963038-Cell Line, Tumor,
pubmed-meshheading:14963038-DNA-Binding Proteins,
pubmed-meshheading:14963038-Enzyme Activation,
pubmed-meshheading:14963038-Epidermal Growth Factor,
pubmed-meshheading:14963038-Focal Adhesion Kinase 2,
pubmed-meshheading:14963038-Genes, Dominant,
pubmed-meshheading:14963038-Genes, Reporter,
pubmed-meshheading:14963038-HeLa Cells,
pubmed-meshheading:14963038-Humans,
pubmed-meshheading:14963038-Immunoblotting,
pubmed-meshheading:14963038-Phosphorylation,
pubmed-meshheading:14963038-Phosphotransferases,
pubmed-meshheading:14963038-Plasmids,
pubmed-meshheading:14963038-Precipitin Tests,
pubmed-meshheading:14963038-Protein-Tyrosine Kinases,
pubmed-meshheading:14963038-Proto-Oncogene Proteins,
pubmed-meshheading:14963038-STAT3 Transcription Factor,
pubmed-meshheading:14963038-Signal Transduction,
pubmed-meshheading:14963038-Trans-Activators,
pubmed-meshheading:14963038-Transfection,
pubmed-meshheading:14963038-Tyrosine
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| pubmed:year |
2004
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| pubmed:articleTitle |
Pyk2 amplifies epidermal growth factor and c-Src-induced Stat3 activation.
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| pubmed:affiliation |
B Cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
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| pubmed:publicationType |
Journal Article
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