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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
Although Jak kinases are essential for initiating cytokine signaling, the role of other nonreceptor tyrosine kinases in this process remains unclear. We have examined the role of Fes in IL-4 signaling. Examination of Jak1-deficient cell lines demonstrates that Jak1 is required for the activation of Fes by IL-4. Experiments studying signaling molecules activated by IL-4 receptor suggest that IL-4 signaling can be subdivided into Fes-dependent and Fes-independent pathways. Overexpression of kinase-inactive Fes blocks the IL-4 activation of insulin receptor substrate-2, but not STAT6. Fes appears to be a downstream kinase from Jak1/Jak3 in this process. Further examination of downstream signaling demonstrates that kinase-inactive Fes inhibits the recruitment of phosphoinositide 3-kinase to the activated IL-4 receptor complex and decreases the activation of p70(S6k) kinase in response to IL-4. This inhibition correlates with a decrease in IL-4-induced proliferation. In contrast, mutant Fes does not inhibit the activation of Akt by IL-4. These data demonstrate that signaling pathways activated by IL-4 require different tyrosine kinases. This differential requirement predicts that specific kinase inhibitors may permit the disruption of specific IL-4-induced functions.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/FES protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fes protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/IRS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Irs2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/JAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Jak1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fes,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
166
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2627-34
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11160325-Animals,
pubmed-meshheading:11160325-B-Lymphocytes,
pubmed-meshheading:11160325-Cell Division,
pubmed-meshheading:11160325-Cell Line,
pubmed-meshheading:11160325-Enzyme Activation,
pubmed-meshheading:11160325-Humans,
pubmed-meshheading:11160325-Insulin Receptor Substrate Proteins,
pubmed-meshheading:11160325-Interleukin-4,
pubmed-meshheading:11160325-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11160325-Janus Kinase 1,
pubmed-meshheading:11160325-Lymphocyte Activation,
pubmed-meshheading:11160325-Mice,
pubmed-meshheading:11160325-Mutagenesis, Site-Directed,
pubmed-meshheading:11160325-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11160325-Phosphoproteins,
pubmed-meshheading:11160325-Phosphorylation,
pubmed-meshheading:11160325-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11160325-Protein-Tyrosine Kinases,
pubmed-meshheading:11160325-Proto-Oncogene Proteins,
pubmed-meshheading:11160325-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11160325-Proto-Oncogene Proteins c-fes,
pubmed-meshheading:11160325-Receptor, Insulin,
pubmed-meshheading:11160325-Ribosomal Protein S6 Kinases,
pubmed-meshheading:11160325-Signal Transduction,
pubmed-meshheading:11160325-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Fes mediates the IL-4 activation of insulin receptor substrate-2 and cellular proliferation.
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pubmed:affiliation |
Department of Medicine and Microbiology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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