PU.1 and Spi-B are required for normal B cell receptor-mediated signal transduction
PU.1 and Spi-B are required for normal B cell receptor-mediated signal transduction
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DOI：
10.1016/s1074-7613(00)80040-0
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发表时间：
1999-04-01
期刊：
影响因子：
32.4
通讯作者：
Simon, MC
中科院分区：
文献类型：
--
作者：
Garrett-Sinha, LA;Su, GH;Simon, MC
PU.1和Spi-B先前被认为与B细胞受体（BCR）信号成分编码基因的调控有关。Spi-B-/- B淋巴细胞对BCR刺激反应较差；然而，PU.1（-/-）小鼠缺乏B细胞，因此无法分析BCR反应。我们现在发现PU.1(+/-)Spi-B-/- B细胞比Spi-B-/- B细胞表现出更广泛的缺陷，这表明PU.1和Spi-B都是正常BCR信号传导所必需的。引人注目的是，BCR交联导致突变B细胞中蛋白酪氨酸磷酸化显著降低。进一步分析表明，在突变细胞中，Ig α被磷酸化，syk被招募并被磷酸化，但BLNK和PLC γ的磷酸化存在缺陷。我们的数据支持存在一种新的组件耦合到下游目标。
PU.1 and Spi-B have previously been implicated in the regulation of genes encoding B cell receptor (BCR) signaling components. Spi-B-/- B lymphocytes respond poorly to BCR stimulation; PU.1(-/-) mice, however, lack B cells, precluding an analysis of BCR responses. We now show that PU.1(+/-)Spi-B-/- B cells exhibit more extensive defects than Spi-B-/- B cells, indicating that both PU.1 and Spi-B are required for normal BCR signaling. Strikingly, BCR cross-linking results in substantially reduced protein tyrosine phosphorylation in mutant B cells. Further analysis shows that Ig alpha is phosphorylated and syk is recruited and becomes phosphorylated but that BLNK and PLC gamma phosphorylation are defective in mutant cells. Our data support the existence of a novel component coupling syk to downstream targets.