v-Src activates both protein kinase C-dependent and independent signaling pathways in murine fibroblasts.
Activating the protein-tyrosine kinase activity of v-Src rapidly induced expression of the two 'primary response' genes, TIS10 and Egr-1, in Balb/c 3T3 cells. Depleting cells of protein kinase C (PKC) by prolonged exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA), blocked v-Src-induced TIS10 expression, but had no effect on v-Src-induced Egr-1 gene expression. In addition, the induction of TIS10 and Egr-1 by v-Src could be distinguished using protein kinase inhibitors. Thus, v-Src induced gene expression in murine fibroblasts via two distinguishable signaling pathways: one dependent upon PKC and another that is independent of PKC. Consistent with the use of PKC-mediated signaling pathway by v-Src in murine fibroblasts, we found that activating the kinase activity of v-Src led to increased phosphorylation of a major PKC substrate. Thus, data presented here suggest that v-Src-induced transformation involves the activation of multiple signalling pathways, one of which requires PKC.
Qureshi
S A
SA
Institute for Biomolecular Structure and Function, Hunter College of The City, University of New York, New York 10021.
Joseph
C K
CK
Rim
M
M
Maroney
A
A
Foster
D A
DA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D004789:Enzyme Activation / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D016391:Genes, src / Q000235:genetics / Q000502:physiology*; D017874:Immediate-Early Proteins; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011741:Pyrimidine Nucleosides / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011741:Pyrimidine Nucleosides; D014157:Transcription Factors; C005699:sangivamycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate