v-Src activates mitogen-responsive transcription factor Egr-1 via serum response elements.
Activating the protein-tyrosine kinase activity of v-Src in murine fibroblasts leads to increased expression of Egr-1, a mitogen-responsive transcription factor. v-Src-induced expression of Egr-1 is independent of protein synthesis and is controlled at the level of transcription. Target sequences responsive to v-Src-induced signals were investigated using deletion mutant and analysis of the Egr-1 promoter. Upstream Egr-1 promoter sequences linked to a reporter gene were cotransfected with a v-Src expression vector into NIH 3T3 cells. v-Src-enhanced gene expression from the Egr-1 promoter was dependent upon the presence of CC(A/T)6GG elements. The CC(A/T)6GG motif forms the core element of serum response elements (SREs) and is the binding site for serum response factor. The Egr-1 promoter sequences responsive to v-Src contained four SREs. Sequential deletion of these SREs reduced v-Src responsiveness to basal transcription levels. A single SRE from this region was able to confer v-Src responsiveness to a heterologous promoter, and a mutation to the CC(A/T)6GG box of this SRE abolished v-Src-enhanced gene expression. Thus, an early response of v-Src-induced intracellular signaling is the transcriptional activation of a growth factor-responsive transcription factor via an SRE.
Qureshi
S A
SA
Institute for Biomolecular Structure and Function, Hunter College City University of New York, New York 10021.
Cao
X M
XM
Sukhatme
V P
VP
Foster
D A
DA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D015345:Oligonucleotide Probes; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D026362:Serum Response Factor; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)