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

Oncogene. 1991 Jul;6(7):1259-68.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cell Line
  • Cloning, Molecular
  • Cycloheximide / pharmacology
  • DNA / genetics
  • Epidermal Growth Factor / pharmacology
  • Fetal Blood
  • Fibroblasts / metabolism*
  • Fusion Proteins, gag-onc / genetics*
  • Gene Expression* / drug effects
  • Genes, src / genetics*
  • Mutation
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Temperature
  • Transcription, Genetic / drug effects

Substances

  • Fusion Proteins, gag-onc
  • RNA, Messenger
  • Phorbol 12,13-Dibutyrate
  • Epidermal Growth Factor
  • DNA
  • Cycloheximide
  • Protein-Tyrosine Kinases
  • v-fps oncogene protein, Fujinami sarcoma virus