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 intra cellular calcium release channel on the endoplasmic reticulum. T cell receptor stimulation triggered a physical association between the nonr eceptor protein tyrosine kinase Fyn and the IP(3)R, which induced tyro sine 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, a ctivation of the IP(3)R by tyrosine phosphorylation may play a role in regulating [Ca2+](i).