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首页> 外文期刊>Molecular and Cellular Biology >The Ras-GTPase-activating protein SH3 domain is required for Cdc2 activation and mos induction by oncogenic Ras in Xenopus oocytes independently of mitogen-activated protein kinase activation.
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The Ras-GTPase-activating protein SH3 domain is required for Cdc2 activation and mos induction by oncogenic Ras in Xenopus oocytes independently of mitogen-activated protein kinase activation.

机译：Ras-GTPase激活蛋白SH3结构域是爪蟾卵母细胞中致癌性Ras诱导Cdc2激活和mos诱导所必需的，而与促细胞分裂剂激活的蛋白激酶激活无关。

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The Ras-GTPase-activating protein (RasGAP) is an important modulator of p21ras - dependent signal transduction in Xenopus oocytes and in mammalian cells. We investigated the role of the RasGAP SH3 domain in signal transduction with a monoclonal antibody against the SH3 domain of RasGaP. This antibody prevented the activation of the maturation-promoting factor complex (cyclin B-p34cdc2) by oncogenic Ras. The antibody appears to be specific because as little as 5 ng injected per oocyte reduced the level of Cdc2 activation by 50% whereas 100 ng of nonspecific immunoglobulin G did not affect Cdc2 activation. The antibody blocked the Cdc2 activation induced by oncogenic Ras but not that induced by progesterone, which acts independently of Ras. A peptide corresponding to positions 317 to 326 of a sequence in the SH3 domain of human RasGAP blocked Cdc2 activation, whereas a peptide corresponding to positions 273 to 305 of a sequence in the N-terminal moiety of the SH3 domain of RasGAP had no effect. The antibody did not block the mitogen-activated protein (MAP) kinase cascade (activation of MAPK/ERK kinase [MEK], MAP kinase, and S6 kinase p90rsk). Surprisingly, injection of the negative MAP kinase mutant protein ERK2 K52R (containing a K-to-R mutation at position 52) blocked the Cdc2 activation induced by oncogenic Ras as well as blocking the activation of MAP kinase. Thus, MAP kinase is also implicated in the regulation of Cdc2 activity. In this study, we further investigated the regulation of the synthesis of the c-mos oncogene product, which is necessary for the activation of Cdc2. We report that the synthesis of the c-mos oncogene product, which is necessary for the activation antibody to the SH3 domain of RasGAP and by injecting the negative MAP kinase mutant protein ERK2 K52R. These results suggest that oncogenic Ras activates two signaling mechanisms: the MAP kinase cascade and a signaling pathway implicating the SH3 domain of RasGAP. These mechanisms might control Mos protein expression implicated in Cdc2 activation.
机译：Ras-GTPase激活蛋白（RasGAP）是非洲爪蟾卵母细胞和哺乳动物细胞中p21ras依赖性信号转导的重要调节剂。我们调查了RasGAP SH3结构域在信号转导中具有针对RasGaP SH3结构域的单克隆抗体的作用。该抗体阻止了致癌性Ras激活成熟促进因子复合物（细胞周期蛋白B-p34cdc2）。该抗体似乎具有特异性，因为每个卵母细胞仅注射5 ng就能将Cdc2激活水平降低50％，而100 ng非特异性免疫球蛋白G不会影响Cdc2激活。该抗体阻断了致癌性Ras诱导的Cdc2活化，但不阻断孕激素诱导的Cdc2活化，而孕酮独立于Ras起作用。对应于人RasGAP的SH3域中序列的317至326位的肽可阻断Cdc2激活，而对应于RasGAP的SH3域的N端部分中的序列273至305位的肽则无效。该抗体没有阻断有丝分裂原活化蛋白（MAP）激酶级联反应（MAPK / ERK激酶[MEK]，MAP激酶和S6激酶p90rsk的激活）。出人意料的是，注射阴性的MAP激酶突变蛋白ERK2 K52R（在位置52处含有K-R突变）阻断了致癌Ras诱导的Cdc2活化，也阻断了MAP激酶的活化。因此，MAP激酶也与Cdc2活性的调节有关。在这项研究中，我们进一步研究了c-mos癌基因产物合成的调控，这对于激活Cdc2是必需的。我们报告的c-mos癌基因产物的合成，这是激活抗体对RasGAP的SH3域并通过注射阴性MAP激酶突变蛋白ERK2 K52R所必需的。这些结果表明致癌性Ras激活两个信号传导机制：MAP激酶级联和牵连RasGAP的SH3域的信号传导途径。这些机制可能控制与Cdc2激活有关的Mos蛋白表达。

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