Role of substrates and products of PI3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav
Role of substrates and products of PI3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav
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DOI：
10.1126/science.279.5350.558
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发表时间：
1998-01-23
期刊：
影响因子：
56.9
通讯作者：
Broek, D
中科院分区：
文献类型：
--
作者：
Han, JW;Luby-Phelps, K;Broek, D
细胞骨架变化和c-jun氨基末端激酶的有丝分裂原刺激由Rac小鸟嘌呤核苷酸结合蛋白Vav介导，Vav是一种Rac的鸟苷二磷酸（GDP）-鸟苷三磷酸（GTP）交换因子，其刺激结合的GDP交换为GTP，结合到磷酸肌醇（PI）3-激酶的底物和产物并直接受其控制。PI 3-激酶底物磷脂酰肌醇-4，5-二磷酸抑制酪氨酸激酶Lck对Vav的激活，而产物磷脂酰肌醇-3，4，5-三磷酸增强Lck对Vav的磷酸化和激活。PI 3-激酶产物对Vav的控制表明Rac的Ras依赖性激活机制。
Mitogen stimulation of cytoskeletal changes and c-jun amino-terminal kinases is mediated by Rac small guanine nucleotide-binding proteins, Vav, a guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange factor for Rac that stimulates the exchange of bound GDP for GTP, bound to and was directly controlled by substrates and products of phosphoinositide (PI) 3-kinase, The PI 3-kinase substrate phosphatidylinositol-4,5-bisphosphate inhibited activation of Vav by the tyrosine kinase Lck, whereas the product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav by Lck. Control of Vav in response to mitogens by the products of PI 3-kinase suggests a mechanism for Ras-dependent activation of Rac.