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Updated: Aug 12, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Role of the Raf/mitogen-activated protein kinase pathway in p21ras desensitization

J K Klarlund1, A D Cherniack, M McMahon

  • 1Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts 01605, USA.

The Journal of Biological Chemistry
|July 12, 1996
PubMed

Insights

Activating the Raf/MAP kinase pathway alone does not disrupt the Son-of-sevenless (Sos) and Grb2 interaction, nor does it inhibit p21(ras) activation by Sos. This suggests other pathways are involved in growth factor-induced desensitization.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Signal transduction

Background:

  • Growth factor stimulation and phorbol ester treatment lead to p21(ras) desensitization.
  • This desensitization is linked to hyperphosphorylation and dissociation of Son-of-sevenless (Sos) from Grb2.

Purpose of the Study:

  • To investigate the role of the Raf/mitogen-activated protein (MAP) kinase pathway in Sos-Grb2 dissociation and p21(ras) activation.

Main Methods:

  • Utilized cells expressing a DeltaRaf-1:ER chimera, activated by estradiol.
  • Assessed Sos phosphorylation, Grb2-Sos interaction, and p21(ras) GTP loading upon stimulation.

Main Results:

  • Estradiol stimulation of DeltaRaf-1:ER activated downstream MEK and MAP kinases, and induced Sos phosphorylation.
  • However, Grb2 dissociation from Sos and impaired p21(ras) activation were not observed upon DeltaRaf-1:ER activation.

Conclusions:

  • Activation of the Raf/MAP kinase pathway alone is insufficient to cause Sos-Grb2 disassembly.
  • The Raf/MAP kinase pathway activation does not interrupt Sos-catalyzed p21(ras) activation.

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