Regulation of the inositol 1,4,5-trisphosphate receptor by tyrosine phosphorylation
Regulation of the inositol 1,4,5-trisphosphate receptor by tyrosine phosphorylation
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DOI：
10.1126/science.272.5267.1492
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发表时间：
1996-06-07
期刊：
影响因子：
56.9
通讯作者：
Marks, AR
中科院分区：
文献类型：
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作者：
Jayaraman, T;Ondrias, K;Marks, AR
酪氨酸激酶通过激活磷脂酶生成1，4，5-三磷酸肌醇(IP3)间接提高细胞内钙离子浓度([Ca~(2+)](I))。IP3激活内质网上的细胞内钙释放通道IP3受体(IP(3)R)。T细胞受体刺激触发了非受体蛋白酪氨酸激酶Fyn和IP(3)R之间的物理联系，从而诱导了IP(3)R的酪氨酸磷酸化。Fyn在体外激活了IP3门控的钙通道，而Fyn(-/-)小鼠胸腺细胞在T细胞激活过程中IP(3)R的酪氨酸磷酸化减少。因此，通过酪氨酸磷酸化激活IP(3)R可能在调节[Ca~(2+)](I)中起作用。
Tyrosine kinases indirectly raise intracellular calcium concentration ([Ca2+](i)) by activating phospholipases that generate inositol 1,4,5-trisphosphate (IP3). IP3 activates the IP3 receptor (IP(3)R), an intracellular calcium release channel on the endoplasmic reticulum. T cell receptor stimulation triggered a physical association between the nonreceptor protein tyrosine kinase Fyn and the IP(3)R, which induced tyrosine phosphorylation of the IP(3)R. Fyn activated an IP3-gated calcium channel in vitro, and tyrosine phosphorylation of the IP(3)R during T cell activation was reduced in thymocytes from fyn(-/-) mice. Thus, activation of the IP(3)R by tyrosine phosphorylation may play a role in regulating [Ca2+](i).