Identification of the site of inhibition of mitogenic signaling by oncogenic ras-p21 by a ras effector peptide

J Protein Chem. 2002 Jul;21(5):367-70. doi: 10.1023/a:1019998403181.

Abstract

We have previously found that a ras switch 1 domain peptide (PNC-7, residues 35-47) selectively blocks oocyte maturation induced by oncogenic (Val 12-containing) ras-p21 protein and also blocks c-raf-induced oocyte maturation. We now find that oncogenic ras-p21 does not inhibit oocyte maturation of a constitutively activated raf protein (raf BXB) that is lacking most of the first 301 amino terminal amino acids, including the major ras binding domain and accessory ras-binding regions. We also find that a dominant negative raf that completely blocks c-raf-induced maturation likewise does not block raf-BXB-induced maturation. We conclude that PNC-7 blocks ras by binding to the amino-terminal domain of raf and that raf BXB must initiate signal transduction in the cytosol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Mitogens / chemistry
  • Mitogens / metabolism
  • Mitogens / pharmacology*
  • Oncogene Protein p21(ras) / antagonists & inhibitors*
  • Oncogene Protein p21(ras) / chemistry
  • Oncogene Protein p21(ras) / metabolism
  • Oncogene Protein p21(ras) / pharmacology*
  • Oocytes / drug effects
  • Oocytes / growth & development
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins c-raf / chemistry*
  • Proto-Oncogene Proteins c-raf / genetics
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Signal Transduction / drug effects*
  • Xenopus laevis

Substances

  • Enzyme Inhibitors
  • Mitogens
  • Peptide Fragments
  • Proto-Oncogene Proteins c-raf
  • Oncogene Protein p21(ras)