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Integrin-dependent activation of the p70 ribosomal S6 kinase signaling pathway

R K Malik1, J T Parsons

  • 1Department of Pediatrics, Health Sciences Center, University of Virginia, Charlottesville, Virginia 22908, USA. jtp@virginia.edu

The Journal of Biological Chemistry
|November 22, 1996
PubMed

Insights

Integrin signaling activates the ribosomal S6 kinase (S6K) pathway in fibroblasts. Focal adhesion kinase (FAK) plays a partial role in this integrin-mediated S6K activation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell surface integrin receptors interact with extracellular matrix proteins, activating intracellular signaling pathways.
  • Focal adhesion kinase (FAK), a protein tyrosine kinase, is involved in integrin signaling and signal transduction.

Purpose of the Study:

  • To investigate the activation of the p70/p85 ribosomal S6 kinase (S6K) pathway by extracellular matrix proteins.
  • To determine the role of phosphatidylinositol 3-kinase (PI3K) and FAK in integrin-mediated S6K activation.

Main Methods:

  • Fibroblast cells were exposed to extracellular matrix proteins.
  • Inhibitors of PI3K (FRAP) and protein tyrosine kinases (herbimycin A, genistein) were used.
  • Overexpression of FAK-related non-kinase (FRNK) was performed in chick embryo cells.

Main Results:

  • Exposure to extracellular matrix proteins activated the S6K pathway in a ligand-dependent manner.
  • PI3K inhibitors blocked integrin-mediated S6K activation.
  • Protein tyrosine kinase inhibitors and FRNK overexpression significantly reduced S6K activation, indicating a role for FAK.

Conclusions:

  • Integrin-mediated activation of S6K is dependent on phosphatidylinositol 3-kinase and protein tyrosine kinase activity.
  • Focal adhesion kinase (FAK) is at least partially required for integrin-mediated S6K activation.

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