Activation of the mitogen-activated protein kinase cascade in response to the temperature inducible expression of v-mos kinase

Cell Growth Differ. 1995 Sep;6(9):1119-27.

Abstract

We have characterized activation of the MAP kinase cascade in an inducible system in response to the temperature-sensitive (ts) expression of the v-mos oncogene. Transformation of immortalized rat embryo fibroblasts by a ts isolate of Moloney murine sarcoma virus (Mo-MuSVts110) constitutively activates MAP kinases (ERK-1 and ERK-2) and MAP kinase kinases (MKK-1 and MKK-2) only at the permissive temperature when v-mos kinase is present and active. Following a shift of the ts-transformed, serum-starved cells from the nonpermissive to permissive temperature, MAP kinases and both MKK-1 and MKK-2 are activated within 1-2 h, concurrent with the reappearance of active mos kinase. Raf-1 kinase activity increases more slowly in response to the reappearance of v-mos, and the mobility shift indicative of hyperphosphorylation was only detected 18 h after the temperature transition. Our data show that MAP kinase cascade activation is an early event following the reappearance of v-mos expression and v-mos kinase activity upon temperature shift, while the first manifestation of morphological transformation appears 24 h after the shift to permissive temperature. These results support the hypothesis that mos acts through the MKK to induce cell transformation.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line, Transformed
  • Enzyme Activation
  • Enzyme Induction
  • Genes, Viral*
  • Genes, mos*
  • Kinetics
  • Proto-Oncogenes
  • Rats
  • Temperature*

Substances

  • Calcium-Calmodulin-Dependent Protein Kinases