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Suppression of integrin activation by activated Ras or Raf does not correlate with bulk activation of ERK MAP kinase

Paul E Hughes1, Beat Oertli, Malene Hansen

  • 1The Division of Vascular Biology, Department of Cell Biology. The Scripps Research Institute, La Jolla, California 92037, USA.

Molecular Biology of the Cell
|July 23, 2002
PubMed

Insights

Ras GTPases regulate integrin activation. H-Ras suppresses integrin activation via Raf-1, independent of ERK MAP kinase, revealing a novel regulatory pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Integrin activation, the modulation of ligand-binding affinity, is crucial for cell adhesion.
  • Ras family small GTP-binding proteins and their effectors regulate integrin activation.
  • H-Ras suppresses integrin activation, while R-Ras promotes it.

Purpose of the Study:

  • To investigate the regulatory mechanisms of integrin activation by Ras GTPases.
  • To identify specific regions of H-Ras involved in integrin activation suppression.
  • To elucidate the role of the ERK MAP kinase pathway in H-Ras-mediated integrin suppression.

Main Methods:

  • Construction and analysis of H-Ras/R-Ras chimeras.
  • Assessment of integrin activation.
  • Evaluation of ERK1/2 MAP kinase pathway activation.
  • Inhibition studies of ERK1/2 MAP kinase.

Main Results:

  • A 35-amino acid region of H-Ras is essential for suppressing integrin activation.
  • H-Ras/R-Ras chimeras suppressing integrin activation showed weak ERK1/2 MAP kinase activation.
  • Inhibition of ERK1/2 MAP kinase did not affect H-Ras or Raf-1 suppression of integrin activation.

Conclusions:

  • Integrin activation suppression by H-Ras is mediated by Raf-1.
  • This suppression is independent of the bulk activation of the ERK MAP kinase pathway.
  • Ras GTPases offer distinct regulatory control over integrin function.

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