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Identification of the site of inhibition of mitogenic signaling by oncogenic ras-p21 by a ras effector peptide |
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| Authors: | Chie Lyndon Friedman Fred K Kung Hsiang-Fu Lin Marie C M Chung Denise Pincus Matthew R |
| Affiliation: | (1) Department of Pathology and Laboratory Medicine, Harbor VA Medical Center, 800 Poly Place, Brooklyn, NY, 11209;(2) Departments of Biology and Chemistry, Long Island University, 1 University Plaza, Brooklyn, NY, 11201;(3) Laboratory of Metabolism, National Cancer Institute, Building 37, Room 4D24, Bethesda, MD, 20892;(4) Institute of Molecular Biology, Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Design and Synthesis, University of Hong Kong, Hong Kong, China;(5) Department of Pathology, SUNY Health Science Center, 450 Clarkson Avenue, Brooklyn, NY, 11203 |
| 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. |
| Keywords: | Oncogenic ras-p21 switch 1 domain 35– 47 peptide constitutively activated raf |
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