Vav1 regulates phospholipase Cγ activation and calcium responses in mast cells
Vav1 regulates phospholipase Cγ activation and calcium responses in mast cells
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DOI：
10.1128/mcb.21.11.3763-3774.2001
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发表时间：
2001-06-01
影响因子：
5.3
通讯作者：
Rivera, J
中科院分区：
文献类型：
--
作者：
Manetz, TS;Gonzalez-Espinosa, C;Rivera, J
造血细胞特异性蛋白质Vav1是酪氨酸激酶的底物，在许多受体（包括Fc β RI）参与后被激活。Vav 1缺陷小鼠含有正常数量的肥大细胞，但比正常小鼠对被动全身过敏反应的反应更弱。尽管FceRI、Syk和LAT（激活T细胞的接头）的酪氨酸磷酸化正常，但Vav 1缺陷型骨髓来源的肥大细胞也表现出脱粒和细胞因子产生减少。相反，磷脂酶C γ 1（PLC γ 1）和PLC γ 2的酪氨酸磷酸化和钙动员显着抑制。用Vav 1重建缺陷型肥大细胞恢复了PLC γ 1和PLC γ 2的正常酪氨酸磷酸化和钙应答。因此，Vav 1对于Fc γ RI介导的肥大细胞中PLC γ的活化和钙动员是必需的。除了其作为Rac 1 GTP酶的活化剂的已知作用之外，这些发现证明了Vav 1作为PLC γ活化的钙信号的调节剂的新功能。
The hematopoietic cell-specific protein Vav1 is a substrate of tyrosine kinases activated following engagement of many receptors, including Fc epsilon RI. Vav1-deficient mice contain normal numbers of mast cells but respond more weakly than their normal counterparts to a passive systemic anaphylaxis challenge. Vav1-deficient bone marrow-derived mast cells also exhibited reduced degranulation and cytokine production, although tyrosine phosphorylation of FceRI, Syk, and LAT (linker for activation of T cells) was normal. In contrast, tyrosine phosphorylation of phospholipase C gamma1 (PLC gamma1) and PLC gamma2 and calcium mobilization were markedly inhibited. Reconstitution of deficient mast cells with Vav1 restored normal tyrosine phosphorylation of PLC gamma1 and PLC gamma2 and calcium responses, Thus, Vav1 is essential to Fc epsilon RI-mediated activation of PLC gamma and calcium mobilization in mast cells, In addition to its known role as an activator of Rac1 GTPases, these findings demonstrate a novel function for Vav1 as a regulator of PLC gamma -activated calcium signals.