Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop
Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop
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DOI：
10.1016/s1097-2765(02)00739-6
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发表时间：
2002-11-01
期刊：
影响因子：
16
通讯作者：
Reth, M
中科院分区：
文献类型：
--
作者：
Rolli, V;Gallwitz, M;Reth, M
我们已经建立了一个协议，允许在果蝇S2施耐德细胞中瞬时和诱导共表达的许多外源基因。利用这种强大的反向遗传学方法，我们研究了蛋白酪氨酸激酶Syk和林恩与B细胞抗原受体（BCR）的相互作用。我们发现，林恩磷酸化的第一个酪氨酸，而Syk磷酸化的BCR免疫受体酪氨酸为基础的激活基序（ITAM）的两个酪氨酸。此外，我们表明，Syk是一个积极的变构酶，这是强烈激活的磷酸化ITAM酪氨酸的结合，从而启动一个正反馈回路的受体。BCR依赖性Syk激活和信号放大被蛋白酪氨酸磷酸酶有效地抵消，其活性受H2O2和细胞内氧化还原平衡的调节。
We have established a protocol allowing transient and inducible coexpression of many foreign genes in Drosophila S2 Schneider cells. With this powerful approach of reverse genetics, we studied the interaction of the protein tyrosine kinases Syk and Lyn with the B cell antigen receptor (BCR). We find that Lyn phosphorylates only the first tyrosine whereas Syk phosphorylates both tyrosines of the BCR immunoreceptor tyrosine-based activation motif (ITAM). Furthermore, we show that Syk is a positive allosteric enzyme, which is strongly activated by the binding to the phosphorylated ITAM tyrosines, thus initiating a positive feedback loop at the receptor. The BCR-dependent Syk activation and signal amplification is efficiently counterbalanced by protein tyrosine phosphatases, the activity of which is regulated by H2O2 and the redox equilibrium inside the cell.