Involvement of p21ras in activation of extracellular signal-regulated kinase 2.
Many growth factors upon stimulation of their receptors induce the activity of extracellular signal-regulated kinases, ERKs, also known as MAP kinases. Several of these growth factors also activate the ras proto-oncogene product, p21ras (Ras), by stimulating the conversion of the inactive GDP-bound form of Ras to the active GTP-bound form. We have shown that direct introduction of p21ras oncoprotein into cells in the absence of growth factors activates ERKs within five minutes, which indicates that normal p21ras may be involved in the activation of ERKs by growth factors. Here we use a recombinant vaccinia virus expressing an interfering mutant of p21ras, RasAsn17, to investigate this question. In NIH3T3 cells that overexpress the insulin receptor, this recombinant virus inhibits insulin-induced activation of ERK2 completely, but there is no inhibition of insulin-induced activation of phosphatidylinositol-3-kinase. In rat-1 cells the recombinant virus inhibited ERK2 activity induced by platelet-derived growth factor (PDGF) but not by phorbol ester. We conclude that p21ras mediates insulin- and PDGF-induced activation of ERK2.
de Vries-Smits
A M
AM
Laboratory for Physiological Chemistry, University of Utrecht, The Netherlands.
Burgering
B M
BM
Leevers
S J
SJ
Marshall
C J
CJ
Bos
J L
JL
D002460:Cell Line; D004274:DNA, Recombinant; D004789:Enzyme Activation / Q000187:drug effects; D011905:Genes, ras; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1; D009154:Mutation; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics
D004274:DNA, Recombinant; D007328:Insulin; C000715470:MAS1 protein, human; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D011494:Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D015689:Oncogene Protein p21(ras); D013755:Tetradecanoylphorbol Acetate