de Vries-Smits A M, Burgering B M, Leevers S J, Marshall C J, Bos J L
Laboratory for Physiological Chemistry, University of Utrecht, The Netherlands.
Nature. 1992 Jun 18;357(6379):602-4. doi: 10.1038/357602a0.
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.
许多生长因子在刺激其受体后会诱导细胞外信号调节激酶（ERK，也称为丝裂原活化蛋白激酶）的活性。其中一些生长因子还通过刺激将无活性的结合GDP形式的Ras转化为有活性的结合GTP形式，来激活原癌基因ras的产物p21ras（Ras）。我们已经表明，在没有生长因子的情况下，将p21ras癌蛋白直接导入细胞会在五分钟内激活ERK，这表明正常的p21ras可能参与生长因子对ERK的激活。在这里，我们使用一种表达p21ras干扰突变体RasAsn17的重组痘苗病毒来研究这个问题。在过表达胰岛素受体的NIH3T3细胞中，这种重组病毒完全抑制胰岛素诱导的ERK2激活，但不抑制胰岛素诱导的磷脂酰肌醇-3-激酶激活。在大鼠-1细胞中，重组病毒抑制血小板衍生生长因子（PDGF）诱导的ERK2活性，但不抑制佛波酯诱导的ERK2活性。我们得出结论，p21ras介导胰岛素和PDGF诱导的ERK2激活。
