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

Research output: Contribution to journal › Article

239 Citations (Scopus)

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

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Focal Adhesion Protein-Tyrosine Kinases
JNK Mitogen-Activated Protein Kinases
G1 Phase
Integrins
Cell Cycle
Enzyme Activation
Growth Factor Receptors
src-Family Kinases
Cell Cycle Checkpoints
Phosphatidylinositol 3-Kinases
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Phosphorylation
Cell Proliferation

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

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

In: Journal of Cell Biology, Vol. 145, No. 7, 28.06.1999, p. 1461-1469.

Research output: Contribution to journal › Article

Oktay, MH, Wary, KK, Dans, M, Birge, RB & Giancotti, FG 1999, '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', Journal of Cell Biology, vol. 145, no. 7, pp. 1461-1469. https://doi.org/10.1083/jcb.145.7.1461
Oktay MH, Wary KK, Dans M, Birge RB, Giancotti FG. 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. Journal of Cell Biology. 1999 Jun 28;145(7):1461-1469. https://doi.org/10.1083/jcb.145.7.1461
Oktay, Maja H. ; Wary, Kishore K. ; Dans, Michael ; Birge, Raymond B. ; Giancotti, Filippo G. / 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. In: Journal of Cell Biology. 1999 ; Vol. 145, No. 7. pp. 1461-1469.
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