Identification of the Site of Inhibition of Oncogenic ras–p21-Induced Signal Transduction by a Peptide from a ras Effector Domain
| Autor: | Ziro Yamaizumi, James M. Chen, Josef Michl, Matthew R. Pincus, Denise L. Chung, Fred K. Friedman, Paul W. Brandt-Rauf, Shazia Amar, Lyndon Chie |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Dominant negative
Peptide Oncogene Protein p21(ras) Biology Inhibitory postsynaptic potential Biochemistry medicine Animals Insulin Bioorganic chemistry chemistry.chemical_classification Effector JNK Mitogen-Activated Protein Kinases JUN kinase Oocyte Molecular biology Peptide Fragments Proto-Oncogene Proteins c-raf medicine.anatomical_structure chemistry Oocytes ras Proteins Female Mitogen-Activated Protein Kinases Signal transduction Signal Transduction |
| Zdroj: | Journal of Protein Chemistry. 18:881-884 |
| ISSN: | 1573-4943 0277-8033 |
| DOI: | 10.1023/a:1020635414089 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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