通过转化和有机氨酸激酶的酸化GAP和GAP相关蛋白质
C Ellis1, M Moran, F McCormick
1Division of Molecular and Developmental Biology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
Nature
|January 25, 1990
概括
蛋白氨酸激酶使用功能性p21ras来信号细胞生长. 这项研究确定了GTPase激活蛋白 (GAP) 和相关蛋白质作为点,将氨酸激酶与细胞转化中的p21ras信号连接起来.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- 信号传导是指信号的传导方式.
背景情况:
- 蛋白氨酸激酶驱动细胞增殖和恶性转变的确切机制尚不清楚.
- 虽然对p21ras的抗体阻断了氨酸激酶的作用,但这些途径之间还没有建立直接的生物化学联系.
- 氨酸激酶中的SH2域调节激酶活性,其在p21ras GTPase激活蛋白 (GAP) 中的存在表明存在潜在的相互作用.
研究的目的:
- 为了研究氨酸激酶和p21ras信号传递之间的生物化学联系.
- 为了确定参与细胞转化中的氨酸激酶的潜在点.
- 阐明SH2域在调解蛋白质-氨酸激酶相互作用中的作用.
主要方法:
- 对p21ras.的抗体进行微注射.
- 对转化细胞中氨酸残留物蛋白质酸化的分析.
- 共同沉测试以确定相互作用的蛋白质.
- 使用可诱导的氨酸激酶表达系统 (v-src,v-fps).
- 用表皮生长因子刺激纤维细胞.
主要成果:
- 发现GTPase激活蛋白 (GAP),p62和p190在细胞中被氨酸酸化,这些细胞被各种氨酸激酶转化.
- 这种氨酸酸化与由v-src和v-fps诱导的细胞转化相关.
- GAP,p62和p190也在响应表皮生长因子刺激时经历了快速的铁酸化.
- 在信号传导途径中,SH2域似乎介导了细胞质蛋白的相互作用.
结论:
- 氨酸激酶可能通过酸化GAP及其相关蛋白质来调节p21ras功能.
- GAP及其合作伙伴被认为是瘤性氨酸激酶和正常生长因子受体的目标.
- 这些发现提供了一种机制,将氨酸激酶活性与p21ras信号传递和细胞转化联系起来,突出显示了SH2域在信号传导中的作用.
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