Involvement of p21^ras in activation of extracellular signal-regulated kinase 2

Abstract

MANY growth factors upon stimulation of their receptors induce the activity of extracellular signal-regulated kinases, ERKs, also known as MAP kinases^1,2. Several of these growth factors also activate the ras proto-oncogene product, p21^ras (Ras), by stimulating the conversion of the inactive GDP-bound form of Ras to the active GTP-bound form^3–6. We have shown that direct introduction of p21^ras oncoprotein into cells in the absence of growth factors activates ERKs within five minutes⁷, which indicates that normal p21^ras may be involved in the activation of ERKs by growth factors. Here we use a recombinant vaccinia virus expressing an interfering mutant of p21^ras, Ras^Asn17, 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 phosphatidyl-inositol-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 p21^ras mediates insulin-and PDGF-induced activation of ERK2.