The stimulation of quiescent rat fibroblasts by v-src and v-fps oncogenic protein-tyrosine kinases leads to the induction of a subset of immediate early genes.
The stimulation of quiescent murine fibroblasts by growth factors and by phorbol esters results in a rapid and transient transcriptional activation of a large group of so-called immediate early genes. Several such genes were found to be induced in chicken embryo fibroblasts following activation of a temperature sensitive (ts) Rous sarcoma virus v-src mutant following temperature shift (Simmons et al., 1989). In contrast, the classical immediate early genes c-myc, c-fos and c-jun were essentially uninducible upon activation of a ts v-src mutant in rat-1 fibroblasts (Welham et al., 1990). We have cloned 9 cDNAs of genes that are rapidly and transiently inducible in rat fibroblasts by ts v-src mutants, and by a ts Fujinami sarcoma virus v-fps mutant. Six of these cDNAs are derived from the known immediate early genes NGFI-A, KC, c-fos, tissue factor, PC4 and ornithine decarboxylase; the other three cDNAs have not been described before. These 9 genes showed individual profiles of inducibility by fetal calf serum, epidermal growth factor (EGF) and by phorbol esters. Their response to the retroviral oncogenic protein-tyrosine kinases correlated best with the one to EGF, suggesting a common pathway of signal transduction. c-fos did not respond strongly to this pathway but was well induced by fetal calf serum. NGFI-A, however, was induced to a similar extent by all activators tested. Furthermore, we demonstrated that the induction of several of these genes by the retroviral oncogenic protein-tyrosine kinases is rapid, direct and occurs at the transcriptional level.
Jähner
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Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186.
Hunter
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D000818:Animals; D002417:Cattle; D002460:Cell Line; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005312:Fetal Blood; D005347:Fibroblasts / Q000378:metabolism*; D015681:Fusion Proteins, gag-onc / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D016391:Genes, src / Q000235:genetics*; D009154:Mutation; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013696:Temperature; D014158:Transcription, Genetic / Q000187:drug effects
D015681:Fusion Proteins, gag-onc; D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D004815:Epidermal Growth Factor; D004247:DNA; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases; C068415:v-fps oncogene protein, Fujinami sarcoma virus