Takata M, Kurosaki T
Department of Oncology and Immunology, Wyeth-Ayerst Research, Pearl River, New York 10965, USA.
J Exp Med. 1996 Jul 1;184(1):31-40. doi: 10.1084/jem.184.1.31.
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.
编码布鲁顿酪氨酸激酶（Btk）的基因缺陷会导致一种名为X连锁无丙种球蛋白血症的疾病，该病中由于B细胞发育受阻，成熟B细胞数量大幅减少。最近的研究表明，Btk在B细胞抗原受体（BCR）刺激后会发生酪氨酸磷酸化并被激活。为了阐明这种激酶的功能，我们检测了缺乏Btk的DT40 B细胞的BCR信号传导。在受体刺激后，突变细胞中磷脂酶C（PLC）-γ2的酪氨酸磷酸化显著降低，导致BCR偶联的磷脂酰肌醇水解和钙动员均丧失。Btk的普列克底物蛋白同源结构域和Src同源结构域2对于PLC-γ2的激活是必需的。由于Syk对于BCR诱导的PLC-γ2激活也是必需的，我们的研究结果表明，PLC-γ2的激活是由Btk和Syk通过协同作用来调节的。
