Identification of the site of inhibition of mitogenic signaling by oncogenic ras-p21 by a ras effector peptide.
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.
Department of Pathology and Laboratory Medicine, Harbor VA Medical Center, Brooklyn, NY 11209, USA.
Lyndon
L
Chie
Fred K
FK
Friedman
Hsiang-Fu
HF
Kung
Marie C M
MC
Lin
Denise
D
Chung
Matthew R
MR
Pincus
D000818:Animals; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008934:Mitogens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015689:Oncogene Protein p21(ras) / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000254:growth & development; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014982:Xenopus laevis
D004791:Enzyme Inhibitors; D008934:Mitogens; D010446:Peptide Fragments; D019908:Proto-Oncogene Proteins c-raf; D015689:Oncogene Protein p21(ras)