Integrin-mediated activation of focal adhesion kinase is required for signaling to Jun NH(2)-terminal kinase and progression through the G1 phase of the cell cycle Journal Article
| Authors: | Oktay, M.; Wary, K. K.; Dans, M.; Birge, R. B.; Giancotti, F. G. |
| Article Title: | Integrin-mediated activation of focal adhesion kinase is required for signaling to Jun NH(2)-terminal kinase and progression through the G1 phase of the cell cycle |
| Abstract: | The extracellular matrix exerts a stringent control on the proliferation of normal cells, suggesting the existence of a mitogenic signaling pathway activated by integrins, but not significantly by growth factor receptors. Herein, we provide evidence that integrins cause a significant and protracted activation of Jun NH2-terminal kinase (JNK), while several growth factors cause more modest or no activation of this enzyme. Integrin-mediated stimulation of JNK required the association of focal adhesion kinase (FAK) with a Src kinase and p130(CAS), the phosphorylation of p130(CAS), and subsequently, the recruitment of Crk. Ras and PI-3K were not required. FAK- JNK signaling was necessary for proper progression through the G1 phase of the cell cycle. These findings establish a role for FAK in both the activation of JNK and the control of the cell cycle, and identify a physiological stimulus for JNK signaling that is consistent with the role of Jun in both proliferation and transformation. |
| Keywords: | signal transduction; protein phosphorylation; human cell; mutation; proto-oncogene proteins; cell proliferation; proteins; protein analysis; animals; mice; cell cycle; cell line; enzyme activation; phosphorylation; extracellular matrix; gene expression regulation; genetic transfection; endothelium, vascular; protein-serine-threonine kinases; phosphoproteins; cell adhesion molecules; binding sites; protein-tyrosine kinases; mitogen-activated protein kinases; cell cycle phase; src-family kinases; cell adhesion; focal adhesion kinase; signal processing; mitogen-activated protein kinase kinases; integrin; cell cycle g1 phase; g1 phase; retinoblastoma-like protein p130; integrins; crk-associated substrate protein; focal adhesion protein-tyrosine kinases; growth substances; jnk mitogen-activated protein kinases; focal adhesion kinase 1; map kinase kinase 4; fibronectins; ca(2+)-calmodulin dependent protein kinase; jun; humans; human; priority journal; article; src homology domains; jun nh2-terminal kinase; proto-oncogene proteins c-crk; control system |
| Journal Title: | Journal of Cell Biology |
| Volume: | 145 |
| Issue: | 7 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Date Published: | 1999-06-28 |
| Start Page: | 1461 |
| End Page: | 1469 |
| Language: | English |
| DOI: | 10.1083/jcb.145.7.1461 |
| PUBMED: | 10385525 |
| PROVIDER: | scopus |
| PMCID: | PMC2133163 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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