Activation of the mitogen-activated protein kinase cascade in response to the temperature inducible expression of v-mos kinase.
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.
Topol
L Z
LZ
Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
Blair
D G
DG
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002461:Cell Line, Transformed; D004789:Enzyme Activation; D004790:Enzyme Induction; D005814:Genes, Viral; D016258:Genes, mos; D007700:Kinetics; D011519:Proto-Oncogenes; D051381:Rats; D013696:Temperature
D017871:Calcium-Calmodulin-Dependent Protein Kinases