Both p21ras and pp60v-src are required, but neither alone is sufficient, to activate the Raf-1 kinase.
| dc.creator | Williams, N G | |
| dc.creator | Roberts, T M | |
| dc.creator | Li, P | |
| dc.date | 1992-04-01 | |
| dc.date.accessioned | 2026-08-03T01:31:15Z | |
| dc.description | The raf genes encode a family of cytoplasmic proteins with intrinsic protein-serine/threonine kinase activity. The c-raf gene is the cellular homolog of v-raf, the transforming gene of murine sarcoma virus 3611. The constitutive kinase activity of the v-Raf protein has been implicated in transformation and mitogenesis. The activity of Raf-1, the protein product of the c-raf gene, is normally suppressed by a regulatory N-terminal domain. Activation of various tyrosine-kinase growth factor receptors results in activation of Raf-1 and its hyperphosphorylation. Further, Raf-1 has been shown to act either downstream or independently of the p21ras protein, as indicated by experiments involving microinjection of anti-Ras antibodies. To investigate the potential role of p21ras in the activation of Raf-1 by tyrosine kinases, we have used the baculovirus/Sf9 cell system to overproduce various wild-type and mutant forms of pp60src, p21ras, and Raf-1 proteins. We show that either pp60v-src or p21c-ras can independently activate the autokinase activity of Raf-1, but only to a limited extent. Surprisingly, both pp60v-src and p21c-ras are required to fully activate Raf-1. Analysis of the Raf-1 autokinase activity in vitro shows that Raf-1 autophosphorylation sites are distributed equally on serine and threonine residues. When Raf-1 is analyzed by immunoblotting, as previously reported for mammalian cell experiments, a marked increase in the apparent molecular weight of Raf-1 is seen only when it is coexpressed with both pp60v-src and p21ras. IMAGES: | |
| dc.identifier | https://pmc.ncbi.nlm.nih.gov/articles/PMC48775/ | |
| dc.identifier | https://pubmed.ncbi.nlm.nih.gov/1372995/ | |
| dc.identifier | https://doi.org/10.1073/pnas.89.7.2922 | |
| dc.identifier.uri | https://repo.dare.co.zw/handle/123456789/155166 | |
| dc.language | en | |
| dc.publisher | National Academy of Sciences | |
| dc.source | Proc Natl Acad Sci U S A | |
| dc.subject | Research Article | |
| dc.title | Both p21ras and pp60v-src are required, but neither alone is sufficient, to activate the Raf-1 kinase. | |
| dc.type | Text |