TYROSINE KINASE-STIMULATED GUANINE-NUCLEOTIDE EXCHANGE ACTIVITY OF VAV IN T-CELL ACTIVATION
TYROSINE KINASE-STIMULATED GUANINE-NUCLEOTIDE EXCHANGE ACTIVITY OF VAV IN T-CELL ACTIVATION
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DOI：
10.1126/science.8484124
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发表时间：
1993-05-07
期刊：
影响因子：
56.9
通讯作者：
ALTMAN, A
中科院分区：
文献类型：
--
作者：
GULBINS, E;COGGESHALL, KM;ALTMAN, A
Vav原癌基因在血液中的表达产物Vav与鸟嘌呤核苷酸释放因子(GRFS)[也称为鸟苷二磷酸解离刺激因子(GDSS)]具有同源性，GRFS激活RAS相关的小三磷酸鸟苷(GTP)结合蛋白。人T细胞裂解物或Vav免疫沉淀物在T细胞抗原受体(TCR)-CD3激活后具有增强的GRF活性；含有推测的GRF结构域的体外翻译的Vav片段也具有活性。TCR-CD3连接后VAV相关的GRF刺激与其酪氨酸磷酸化平行；两者都被蛋白酪氨酸激酶(PTK)抑制剂阻断。Vav也是p56lck PTK的底物。因此，Vav是一种受PTK调控的GRF，它可能通过激活RAS在TCR-CD3启动的信号转导中发挥重要作用。
The hematopoietically expressed product of the vav proto-oncogene, Vav, shares homology with guanine nucleotide releasing factors (GRFs) [also called guanosine diphosphate-dissociation stimulators (GDSs)] that activate Ras-related small guanosine triphosphate (GTP)-binding proteins. Human T cell lysates or Vav immunoprecipitates possessed GRF activity that increased after T cell antigen receptor (TCR)-CD3 triggering; an in vitro-translated Vav fragment that contained the putative GRF domain was also active. Vav-associated GRF stimulation after TCR-CD3 ligation paralleled its tyrosine phosphorylation; both were blocked by a protein tyrosine kinase (PTK) inhibitor. Vav also was a substrate for the p56lck PTK. Thus, Vav is a PTK-regulated GRF that may be important in TCR-CD3-initiated signal transduction through the activation of Ras.