Amplification of B Cell Antigen Receptor Signaling by a Syk/ITAM Positive Feedback Loop

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• 作者：Vé ; ronique Rolli ; Maike Gallwitz ; Thomas Wossning ; Alexandra Flemming ; Wolfgang W. A. Schamel ; Christa Zü ; rn and Michael Reth
• 刊名：Molecular Cell
• 出版年：2002
• 期刊代码：111_10972765
• 类别：bio
• 出版时间：November 2002
• 卷：10
• 期：5
• 页码：1057-1069
• 文件大小：608 K

摘要

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.