Inositol trisphosphate receptor: Phosphorylation by protein kinase C and calcium calmodulin-dependent protein kinases in reconstituted lipid vesicles

We have previously demonstrated that the inositol 1,4,5-trisphosphate (IP₃) receptor is phosphorylated by cyclic AMP-dependent protein kinase (PKA). In the present study, phosphorylation of IP₃ receptors has been examined with purified receptor protein reconstituted in liposomes to remove detergent that can inhibit protein kinases. The IP₃ receptor is stoichiometrically phosphorylated by protein kinase C (PKC) and Ca²⁺ calmodulin-dependent protein kinase II (CaM kinase II) as well as by PKA. Phosphorylation by the three enzymes is additive and involves different peptide sequences. Phosphorylation by PKC, which is stimulated by Ca²⁺ and diacylglycerol, and by CaM kinase II, which requires Ca²⁺, provides means whereby Ca²⁺ and diacylglycerol, formed during inositol phospholipid turnover, may regulate IP₃ receptor physiology.