Regulation of the Inositol 1,4,5-Trisphosphate Receptor by Tyrosine Phosphorylation

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Science  07 Jun 1996:
Vol. 272, Issue 5267, pp. 1492-1494
DOI: 10.1126/science.272.5267.1492


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 (IP3R), 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 IP3R, which induced tyrosine phosphorylation of the IP3R. Fyn activated an IP3-gated calcium channel in vitro, and tyrosine phosphorylation of the IP3R during T cell activation was reduced in thymocytes from fyn−/− mice. Thus, activation of the IP3R by tyrosine phosphorylation may play a role in regulating [Ca2+]i.