Activation of gene expression by a non-transforming unmyristylated-SH3-deleted mutant of Src is dependent upon Tyr-527.
v-Src transcriptionally induces gene expression by activating several transcriptional response elements such as the serum response element (SRE), the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element (TRE), and the c-AMP response element (CRE) found in the promoters of several proliferation-related immediate early genes. We report here that a Src protein, with a deletion in the SH3 domain and lacking a membrane localization signal, strongly activates gene expression mediated by SRE, TRE and CRE transcriptional control elements. This mutant was unable to cause cellular transformation, suggesting that activation of these transcriptional control elements is not sufficient for the induction of a transformed phenotype by Src. Interestingly, the ability of the membrane localization and SH3 deletion mutant to activate gene expression was abolished upon conversion of the C-terminal inhibitory Tyr-527 to Phe. These data suggest the existence of previously unreported Tyr-527-dependent activation of intracellular signals that activate gene expression. These data raise the possibility that Src may exert physiological effects via an interaction between Tyr-527 and an SH2-containing protein that would interact with the phosphorylated form of Tyr-527.
Curto
M
M
Department of Biological Sciences, Hunter College, City University of New York 10021, USA.
Carrero
A
A
Frankel
P
P
Foster
D A
DA
D016475:3T3 Cells; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early; D051379:Mice; D016254:Mutagenesis, Insertional; D009227:Myristic Acids / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion; D026362:Serum Response Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014170:Transformation, Genetic; D014443:Tyrosine / Q000235:genetics*; D018909:src Homology Domains / Q000235:genetics*; D019061:src-Family Kinases
D004268:DNA-Binding Proteins; D009227:Myristic Acids; D009687:Nuclear Proteins; D026362:Serum Response Factor; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D013755:Tetradecanoylphorbol Acetate