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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
20
|
| pubmed:dateCreated |
1997-6-19
|
| pubmed:abstractText |
Cell adhesion to extracellular matrix proteins such as fibronectin (FN) triggers a number of intracellular signaling events including the increased tyrosine phosphorylation of the cytoplasmic focal adhesion protein-tyrosine kinase (PTK) and also the stimulation of the mitogen-activated protein kinase ERK2. Focal adhesion kinase (FAK) associates with integrin receptors, and FN-stimulated phosphorylation of FAK at Tyr-397 and Tyr-925 promotes the binding of Src family PTKs and Grb2, respectively. To investigate the mechanisms by which FAK, c-Src, and Grb2 function in FN-stimulated signaling events to ERK2, we expressed wild type and mutant forms of FAK in human 293 epithelial cells by transient transfection. FAK overexpression enhanced FN-stimulated activation of ERK2 approximately 4-fold. This was blocked by co-expression of the dominant negative Asn-17 mutant Ras, indicating that FN stimulation of ERK2 was Ras-dependent. FN-stimulated c-Src PTK activity was enhanced by wild type FAK expression, whereas FN-stimulated activation of ERK2 was blocked by expression of the c-Src binding site Phe-397 mutant of FAK. Expression of the Grb2 binding site Phe-925 mutant of FAK enhanced activation of ERK2, whereas a kinase-inactive Arg-454 mutant FAK did not. Expression of wild type and Phe-925 FAK, but not Phe-397 FAK, enhanced p130(Cas) association with FAK, Shc tyrosine phosphorylation, and Grb2 binding to Shc after FN stimulation. FN-induced Grb2-Shc association is another pathway leading to activation of ERK2 via Ras. The inhibitory effects of Tyr-397 FAK expression show that FAK-mediated association and activation of c-Src is essential for maximal signaling to ERK2. Moreover, multiple signaling pathways are activated upon the formation of an FAK.c-Src complex, and several of these can lead to Ras-dependent ERK2 mitogen-activated protein kinase activation.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Protein-Tyrosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/PTK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins pp60(c-src),
http://linkedlifedata.com/resource/pubmed/chemical/Ptk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
16
|
| pubmed:volume |
272
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
13189-95
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9148935-Animals,
pubmed-meshheading:9148935-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9148935-Cell Adhesion,
pubmed-meshheading:9148935-Cell Adhesion Molecules,
pubmed-meshheading:9148935-Cell Line,
pubmed-meshheading:9148935-Enzyme Activation,
pubmed-meshheading:9148935-Focal Adhesion Kinase 1,
pubmed-meshheading:9148935-Focal Adhesion Protein-Tyrosine Kinases,
pubmed-meshheading:9148935-Humans,
pubmed-meshheading:9148935-Integrins,
pubmed-meshheading:9148935-Mice,
pubmed-meshheading:9148935-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:9148935-Protein-Tyrosine Kinases,
pubmed-meshheading:9148935-Proto-Oncogene Proteins pp60(c-src),
pubmed-meshheading:9148935-Signal Transduction,
pubmed-meshheading:9148935-Transfection,
pubmed-meshheading:9148935-ras Proteins
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to ERK2/mitogen-activated protein kinase through interactions with and activation of c-Src.
|
| pubmed:affiliation |
Salk Institute for Biological Studies, Molecular Biology and Virology Laboratory, La Jolla, California 92037, USA. dschlaep@scripps.edu
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|