Integrin-mediated activation of focal adhesion kinase is required for signaling to Jun NH2-terminal kinase and progression through the G1 phase of the cell cycle

Maja Oktay, Kishore K. Wary, Michael Dans, Raymond B. Birge, Filippo G. Giancotti

Research output: Contribution to journalArticle

239 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1461-1469
Number of pages9
JournalJournal of Cell Biology
Volume145
Issue number7
DOIs
StatePublished - Jun 28 1999
Externally publishedYes

Keywords

  • Cell cycle
  • Focal adhesion kinase
  • Integrins
  • Jun
  • Jun NH-terminal kinase

ASJC Scopus subject areas

  • Cell Biology

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