An inhibitory mutant of c-Raf-1 blocks v-Src-induced activation of the Egr-1 promoter.
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.
Institute for Biomolecular Structure and Function, Hunter College, City University of New York, New York 10021.
S A
SA
Qureshi
M
M
Rim
J
J
Bruder
W
W
Kolch
U
U
Rapp
V P
VP
Sukhatme
D A
DA
Foster
D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins; D066298:In Vitro Techniques; D051379:Mice; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019908:Proto-Oncogene Proteins c-raf; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D015688:Oncogene Protein pp60(v-src); D019908:Proto-Oncogene Proteins c-raf