Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation
Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation
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DOI：
10.1084/jem.20011571
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发表时间：
2002-01-21
影响因子：
15.3
通讯作者：
Kurosaki, T
中科院分区：
文献类型：
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作者：
Inabe, K;Ishiai, M;Kurosaki, T
为了阐明Vav家族蛋白质的新成员Vav 3参与B细胞抗原受体（BCR）信号传导的机制，我们产生了Vav 3缺陷的B细胞系。在这里，我们报告说，Vav 3影响磷脂酰肌醇3-激酶（PI3K）的功能，通过Rac 1的磷脂酰肌醇-3，4，5-三磷酸（PIP3）代海衰减的损失Vav 3或表达的显性负性形式的Rac 1。PI3K和Rac1之间的功能性相互作用也通过在GTP结合的Rac1存在下PI3K活性增加来证明。此外，ss-e显示Vav 3缺陷细胞中钙动员酸性c-Jun NH2-末端激酶（JNK）活化的缺陷通过缺失PIP3水解酶、含SH 2结构域的肌醇多磷酸5 '-磷酸酶（SHIP）而减轻。因此，我们的结果表明Vav 3通过促进PIP3的持续产生并由此促进钙流而在调节B细胞应答中起作用。
To elucidate the mechanism(s) by which Vav3, a new member of the Vav family proteins, participates in B cell antigen receptor (BCR) signaling, we have generated a B cell line deficient in Vav3. Here we report that Vav3 influences phosphoinositide 3-kinase (PI3K) function through Rac1 in that phosphatidylinositol-3,4,5-trisphosphate (PIP3) generation seas attenuated by loss of Vav3 or by expression of a dominant negative form of Rac1 . The functional interaction between PI3K and Rac1 was also demonstrated by increased PI3K activity in the presence of GTP-bound Rac1. In addition, ss-e show that defects of calcium mobilization acid c-Jun NH2- terminal kinase (JNK) activation in Vav3-deficient cells are relieved by deletion of a PIP3 hydrolyzing enzyme, SH2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP). Hence, our results suggest a role for Vav3 in regulating the B cell responses by promoting the sustained production of PIP3 and thereby calcium flux.