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Involvement of p21ras in activation of extracellular signal-regulated kinase 2

A M de Vries-Smits1, B M Burgering, S J Leevers

  • 1Laboratory for Physiological Chemistry, University of Utrecht, The Netherlands.

Nature
|June 18, 1992
PubMed

Insights

Ras proto-oncogene product (Ras) activation of extracellular signal-regulated kinases (ERKs) is crucial for growth factor signaling. Ras mediates insulin and platelet-derived growth factor (PDGF)-induced ERK activation.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Oncogene research

Background:

  • Growth factors activate extracellular signal-regulated kinases (ERKs), also known as MAP kinases.
  • Growth factors also activate p21ras (Ras) by promoting its conversion from GDP-bound to GTP-bound form.
  • Direct introduction of p21ras oncoprotein activates ERKs rapidly, suggesting its role in growth factor signaling.

Purpose of the Study:

  • To investigate the role of p21ras in mediating growth factor-induced ERK activation.
  • To determine if Ras is a common mediator for different growth factor signaling pathways.

Main Methods:

  • Utilized a recombinant vaccinia virus expressing an interfering mutant of p21ras (RasAsn17).
  • Assessed the effect of RasAsn17 on insulin-induced ERK2 and phosphatidylinositol-3-kinase activation in NIH3T3 cells.
  • Examined the impact of RasAsn17 on ERK2 activity induced by platelet-derived growth factor (PDGF) and phorbol ester in rat-1 cells.

Main Results:

  • RasAsn17 completely inhibited insulin-induced ERK2 activation in NIH3T3 cells overexpressing the insulin receptor.
  • RasAsn17 did not inhibit insulin-induced phosphatidylinositol-3-kinase activation.
  • RasAsn17 inhibited PDGF-induced ERK2 activity in rat-1 cells but not phorbol ester-induced ERK2 activity.

Conclusions:

  • p21ras (Ras) is a critical mediator in the signaling pathways for insulin and PDGF.
  • Ras specifically mediates the activation of ERK2 by these growth factors.
  • The findings highlight Ras's central role in linking specific growth factor receptors to ERK activation.

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