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Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Corbit, Kevin C. Trakul, Nicholas Eves, Eva M. Diaz, Bruce Marshall, Mark Rosner, Marsha Rich |
| Copyright Year | 2003 |
| Abstract | Protein kinase C (PKC) regulates activation of the Raf-1 signaling cascade by growth factors, but the mechanism by which this occurs has not been elucidated. Here we report that one mechanism involves dissociation of Raf kinase inhibitory protein (RKIP) from Raf-1. Classic and atypical but not novel PKC isoforms phosphorylate RKIP at serine 153 (Ser-153). RKIP Ser-153 phosphorylation by PKC either in vitro or in response to 12-O-tetradecanoylphorbol-13-acetate or epidermal growth factor causes release of RKIP from Raf-1, whereas mutant RKIP (S153V or S153E) remains bound. Increased expression of PKC can rescue inhibition of the mitogen-activated protein (MAP) kinase signaling cascade by wild-type but not mutant S153V RKIP. Taken together, these results constitute the first model showing how phosphorylation by PKC relieves a key inhibitor of the Raf/MAP kinase signaling cascade and may represent a general mechanism for the regulation of MAP kinase pathways. |
| Starting Page | 046601 |
| Ending Page | 046601 |
| Page Count | 1 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jbc.org/content/278/15/13061.full.pdf |
| Alternate Webpage(s) | http://www.jbc.org/content/early/2003/01/27/jbc.M210015200.full.pdf |
| PubMed reference number | 12551925v1 |
| Volume Number | 278 |
| Issue Number | 15 |
| Journal | The Journal of biological chemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Cascade Device Component Growth Factor Mitogens PEBP1 gene Protein Isoforms Protein Kinase C Protein Kinases RAF1 wt Allele Tetradecanoylphorbol Acetate |
| Content Type | Text |
| Resource Type | Article |
