Inhibition of v-raf-dependent c-fos expression and transformation by a kinase-defective mutant of the mitogen-activated protein kinase Erk2.

摘要: Receptor-bound growth factors elicit intracellular signals that lead to the phosphorylation and activation of numerous kinases transcription with consequent changes in patterns gene expression. Several oncogene products are able mimic these signals, resulting cell transformation proliferation. For example, introduction oncogenic forms Raf-1 kinase into fibroblasts induces leads constitutive expression of, among others, c-fos proto-oncogene. Here it is shown elevation promoter activity brought about by v-raf mediated TCF/Elk-1, which a ternary complex SRF at serum response element substrate for mitogen-activating protein vitro. In NIH 3T3 fibroblasts, activates Erk2, overexpression an interfering mutant Erk2 both blocks ability activate suppresses transformation. Mutation individual phosphoacceptor sites TCF/Elk-1 also compromises v-raf-activated Gal-Elk/Gal-chloramphenicol acetyltransferase reporter system. However, least one instance glutamate, but not aspartate, site compatible activation. These results provide compelling evidence major link kinase-dependent signal transduction pathway