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Inhibition of Oncogenic and Activated Wild-Type ras-p21 Protein-Induced Oocyte Maturation by Peptides from the Guanine-Nucleotide Exchange Protein, SOS, Identified from Molecular Dynamics Calculations. Selective Inhibition of Oncogenic ras-p21
Journal article   Peer reviewed

Inhibition of Oncogenic and Activated Wild-Type ras-p21 Protein-Induced Oocyte Maturation by Peptides from the Guanine-Nucleotide Exchange Protein, SOS, Identified from Molecular Dynamics Calculations. Selective Inhibition of Oncogenic ras-p21

Lyndon Chie, James Chen, Fred Friedman, Denise Chung, Shazia Amar, Josef Michl, Z Yamaizumi, Paul Brandt-rauf and Matthew Pincus
Journal of protein chemistry, v 18(8), pp 875-879
01 Nov 1999
PMID: 10839624

Abstract

Genomics Molecular biology Peptides Proteins Signal transduction
In the preceding paper we performed molecular dynamics calculations of the average structures of the SOS protein bound to wild-type and oncogenic ras-p21. Based on these calculations, we have identified four major domains of the SOS protein, consisting of residues 631-641, 676-691, 718-729, and 994-1004, which differ in structure between the two complexes. We have now microinjected synthetic peptides corresponding to each of these domains into Xenopus laevis oocytes either together with oncogenic (Val 12)-p21 or into oocytes subsequently incubated with insulin. We find that the first three peptides inhibit both oncogenic and wild-type p21-induced oocyte maturation, while the last peptide much more strongly inhibits oncogenic p21 protein-induced oocyte maturation. These results suggest that each identified SOS region is involved in ras-stimulated signal transduction and that the 994-1004 domain is involved uniquely with oncogenic ras-p21 signaling.[PUBLICATION ABSTRACT]

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