ASSOCIATION BETWEEN GTPASE ACTIVATORS FOR RHO AND RAS FAMILIES
ASSOCIATION BETWEEN GTPASE ACTIVATORS FOR RHO AND RAS FAMILIES
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DOI：
10.1038/359153a0
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发表时间：
1992-09-10
期刊：
影响因子：
64.8
通讯作者：
WEINBERG, RA
中科院分区：
文献类型：
--
作者：
SETTLEMAN, J;ALBRIGHT, CF;WEINBERG, RA
ras相关的低分子量GTP酶参与涉及多种细胞功能的信号转导，包括细胞周期进程、细胞分化、细胞骨架组织、蛋白质转运和分泌1 -2。这些蛋白质在GTP结合和GDP结合状态之间的循环部分地由刺激特异性GTP酶1 -6的内在GTP水解活性的GTP酶激活蛋白（GAP）控制。在生长因子刺激和酪氨酸激酶转化的细胞中，ras GTP酶激活蛋白（Ras-GAP）与第二种蛋白质p190（M（r）190，000）形成复合物7，8。在其羧基末端，p190含有在断点簇区域、n-嵌合蛋白和Rho-GAP 9中保守的区域。这三种蛋白质中的每一种都对小GTP酶的rho家族的至少一个成员表现出GAP活性10。我们已经测试了重组p190蛋白对ras、rho和rab家族的GTP酶的GAP活性，并在此表明p190可以作为特异性针对rho家族成员的GAP起作用。因此，在生长因子刺激的细胞中Ras-GAP和p190之间的复合物的形成可能允许涉及ras和rho GTP酶的信号通路的偶联。
THE ras-related low-molecular-mass GTPases participate in signal transduction involving a variety of cellular functions, including cell-cycle progression, cellular differentiation, cytoskeletal organization, protein transport and secretion1-2. The cycling of these proteins between GTP-bound and GDP-bound states is partially controlled by GTPase activating proteins (GAPs) which stimulate the intrinsic GTP-hydrolysing activity of specific GTPases1-6. The ras GTPase-activating protein (Ras-GAP) forms a complex with a second protein, p190 (M(r) 190,000), in growth-factor stimulated and tyrosine-kinase transformed cells7,8. At its carboxy-terminal end, p190 contains a region that is conserved in the breakpoint cluster region, n-chimaerin, and Rho-GAP9. Each of these three proteins exhibits GAP activity for at least one member of the rho family of small GTPases10. We have tested recombinant p190 protein for GAP activity on GTPases of the ras, rho and rab families, and show here that p190 can function as a GAP specifically for members of the rho family. Consequently, the formation of a complex between Ras-GAP and p190 in growth-factor stimulated cells may allow the coupling of signalling pathways that involve ras and rho GTPases.