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J. Biol. Chem., Vol. 266, Issue 31, 20594-20597, Nov, 1991
SA Qureshi, M Rim, J Bruder, W Kolch, U Rapp, VP Sukhatme and DA Foster
Institute for Biomolecular Structure and Function, Hunter College, City University of New York, New York 10021.
The protein-tyrosine kinase activity of v-Src leads to the transcriptional activation of the mitogen-responsive transcription factor Egr-1. c-Raf-1 is a serine/threonine protein kinase that has been implicated in the transduction of signals induced by mitogens. The involvement of c-Raf-1 in v-Src-induced Egr-1 expression was investigated using an inhibitory mutant of c-Raf-1. We report here that expression of a kinase-defective mutant of c-Raf-1 inhibits v-Src- induced activation of the Egr-1 promoter. This inhibition is reversed by overexpression of wild type c-Raf-1. Consistent with an involvement of c-Raf-1 in a signaling pathway leading to Egr-1 expression, we find that v-Raf induces Egr-1 promoter activation. These data suggest that c- Raf-1 is a component in an intracellular signaling pathway initiated by v-Src leading to the induction of the mitogen-responsive transcription factor Egr-1.
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