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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MSK Authors
  1. Maja H Oktay
    4 Oktay
  2. Michael J Dans
    9 Dans
  3. Kishore K Wary
    8 Wary