Functional interaction of Src family kinases with the acetylcholine receptor in C2 myotubes
Functional interaction of Src family kinases with the acetylcholine receptor in C2 myotubes
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DOI：
10.1074/jbc.271.50.32474
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发表时间：
1996-12-13
影响因子：
4.8
通讯作者：
Hall, ZW
中科院分区：
文献类型：
--
作者：
Fuhrer, C;Hall, ZW
据推测，乙酰胆碱受体 (AChR) β 亚基的酪氨酸磷酸化在神经肌肉接头发育过程中的 AChR 聚集中发挥作用。我研究了哺乳动物 C2 肌管中这种磷酸化的机制，并报告酪氨酸激酶 Src 结合并磷酸化含有 β 亚基胞质环 N 端一半的谷胱甘肽 S 转移酶融合蛋白。不会与相关激酶 Fyn 或 Yes 或与 γ 和 δ 亚基的相应区域发生结合。此外，使用α-银环蛇毒素-Sepharose 从 C2 肌管亲和分离的 AChR 仅与 Src 和 Fyn 特异性相关，并具有酪氨酸磷酸化的 β 亚基。我们认为 AChR 最初被 Src 磷酸化，随后以磷酸酪氨酸依赖性方式结合 Fyn。这些相互作用可能在突触发生过程中特化突触后膜的构建中发挥重要作用。
Tyrosine phosphorylation of the beta subunit of the acetylcholine receptor (AChR) has been postulated to play a role in AChR clustering during development of the neuromuscular junction. me have investigated the mechanism of this phosphorylation in mammalian C2 myotubes and report that the tyrosine kinase Src binds and phosphorylates glutathione S-transferase fusion proteins containing the N-terminal half of the cytoplasmic loop of the beta subunit. No binding occurs to the related kinases Fyn or Yes or to the corresponding regions from the gamma and delta subunits. Furthermore, AChRs affinity-isolated from C2 myotubes using alpha-bungarotoxin-Sepharose mere specifically associated with Src and Fyn and had tyrosine-phosphorylated beta subunits. We suggest that AChRs are initially phosphorylated by Src and subsequently bind Fyn in a phosphotyrosine-dependent manner. These interactions are likely to play an important role in construction of the specialized postsynaptic membrane during synaptogenesis.