A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2.
A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2.
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DOI：
10.1084/jem.184.1.31
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发表时间：
1996-07-01
期刊：
影响因子：
--
通讯作者：
Kurosaki T
中科院分区：
文献类型：
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作者：
Takata M;Kurosaki T
编码布鲁顿酪氨酸激酶（Btk）的基因缺陷导致一种称为X连锁无丙种球蛋白血症的疾病，其中由于B细胞发育受阻而导致成熟B细胞严重减少。最近的研究表明，Btk是酪氨酸磷酸化和激活后，B细胞抗原受体（BCR）的刺激。为了阐明这种激酶的功能，我们检测了Btk缺陷的DT 40 B细胞的BCR信号。在突变细胞中，受体刺激后磷脂酶C（PLC）-γ 2的酪氨酸磷酸化显著降低，导致BCR偶联磷脂酰肌醇水解和钙动员的丧失。PLC-γ 2激活需要Btk的Pleckstrin同源性和Src-同源性2结构域。由于Syk也是BCR诱导的PLC-γ 2激活所必需的，因此我们的研究结果表明PLC-γ 2激活受Btk和Syk通过其协同作用调节。
Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-gamma 2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCR-coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-gamma 2 activation. Since Syk is also required for the BCR-induced PLC-gamma 2 activation, our findings indicate that PLC-gamma 2 activation is regulated by Btk and Syk through their concerted actions.