A NONRECEPTOR TYROSINE KINASE THAT INHIBITS THE GTPASE ACTIVITY OF P21(CDC42)
A NONRECEPTOR TYROSINE KINASE THAT INHIBITS THE GTPASE ACTIVITY OF P21(CDC42)
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DOI：
10.1038/363364a0
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发表时间：
1993-05-27
期刊：
影响因子：
64.8
通讯作者：
LIM, L
中科院分区：
文献类型：
--
作者：
MANSER, E;LEUNG, T;LIM, L
GTP结合蛋白（p21）的Ras相关Rho亚家族，包括Rho、Rac和Cdc 42 Hs，涉及细胞骨架组织的不同方面1，2。这些蛋白质的行为类似于Ras（p21 ras），因为它们的活性GTP结合形式通过核苷酸γ-磷酸的内在水解而失活，而核苷酸γ-磷酸可以被GTP酶激活蛋白（GAP）刺激。我们以前已经表明，有一个GAP的多样性，识别这个亚家族3，包括n-chimaerin，这是丰富的campus 4;我们还检测到蛋白质结合这些p21蛋白，似乎抑制GTP水解。我们现在报告的表征海马互补DNA编码的酪氨酸激酶，特异性结合Cdc 42 Hs在其GTP结合的形式。这种结合是由一个独特的47个氨基酸的序列的C-末端的SH 3结构域介导的，并抑制固有的和GAP刺激的GT3活性的Cdc 42 Hs。我们的研究结果表明，可能有一个监管机制，维持GTP结合的活性形式的Cdc 42 Hs，这是直接连接到酪氨酸磷酸化途径。
THE Ras-related Rho subfamily of GTP-binding proteins (p21s), which includes Rho, Rac and Cdc42Hs, is implicated in different aspects of cytoskeletal organization1,2. These proteins behave like Ras (p21ras) in that their active GTP-bound form is inactivated by intrinsic hydrolysis of the nucleotide gamma-phosphate, which can be stimulated by GTPase-activating proteins (GAPs). We have previously shown that there is a diversity of GAPs that recognize this subfamily3, including n-chimaerin, which is enriched in the hippocampus4; we also detected proteins that bind these p21 proteins and seem to inhibit GTP hydrolysis. We now report the characterization of a hippocampal complementary DNA encoding a tyrosine kinase that specifically binds Cdc42Hs in its GTP-bound form. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain and inhibits both the intrinsic and GAP-stimulated GTPase activity of Cdc42Hs. Our findings indicate that there may be a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation pathway.