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Identification of the Site of Inhibition of Oncogenic ras-p21-Induced Signal Transduction by a Peptide from a ras Effector Domain
Journal article   Peer reviewed

Identification of the Site of Inhibition of Oncogenic ras-p21-Induced Signal Transduction by a Peptide from a ras Effector Domain

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 881-884
01 Nov 1999
PMID: 10839625

Abstract

Genomics Kinases Molecular biology Peptides Proteins Signal transduction
We have previously found that a peptide corresponding to residues 35-47 of the ras-p21 protein, from its switch 1 effector domain region, strongly inhibits oocyte maturation induced by oncogenic p21, but not by insulin-activated cellular wild-type p21. Another ras-p21 peptide corresponding to residues 96-110 that blocks ras-jun and jun kinase (JNK) interactions exhibits a similar pattern of inhibition. We have also found that c-raf strongly induces oocyte maturation and that dominant negative c-raf strongly blocks oncogenic p21-induced oocyte maturation. We now find that the p21 35-47, but not the 96-110, peptide completely blocks c-raf-induced maturation. This finding suggests that the 35-47 peptide blocks oncogenic ras at the level of raf; that activated normal and oncogenic ras-p21 have differing requirements for raf-dependent signaling; and that the two oncogenic-ras-selective inhibitory peptides, 35-47 and 96-110, act at two different critical downstream sites, the former at raf, the latter at JNK/jun, both of which are required for oncogenic ras-p21 signaling.[PUBLICATION ABSTRACT]

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