Regulation of the inositol 1,4,5-trisphosphate receptor by tyrosine phosphorylation

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).