Inositol 1,4,5-trisphosphate receptor type 1 phosphorylation and regulation by extracellular signal-regulated kinase

Type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) is a widely expressed intracellular calcium-release channel found in many cell types. The operation of IP3R1 is regulated through phosphorylation by multiple protein kinases. Extracellular signal-regulated kinase (ERK) has been found involved in calcium signaling in distinct cell types, but the underlying mechanisms remain unclear. Here, we present evidence that ERK1/2 and IP3R1 bind together through an ERK binding motif in mouse cerebellum in vivo as well as in vitro. ERK-phosphorylating serines (Ser 436) was identified in mouse IP3R1 and Ser 436 phosphorylation had a suppressive effect on IP3 binding to the recombinant N-terminal 604-amino acid residues (N604). Moreover, phosphorylation of Ser 436 in R(224–604) evidently enhance its interaction with the N-terminal “suppressor” region (N223). At last, our data showed that Ser 436 phosphorylation in IP3R1 decreased Ca2+ releasing through IP3R1 channels.