Modulation of inositol 1,4,5-trisphosphate receptor type 2 channel activity by Ca2+/calmodulin-dependent protein kinase II (CaMKII)-mediated phosphorylation.

ABSTRACT: InsP(3)-mediated calcium release through the type 2 inositol 1,4,5-trisphosphate receptor (InsP(3)R2) in cardiac myocytes results in the activation of associated CaMKII, thus enabling the kinase to act on downstream targets, such as histone deacetylases 4 and 5 (HDAC4 and HDAC5). The CaMKII activity also feedback modulates InsP(3)R2 function by direct phosphorylation and results in a dramatic decrease in the receptor-channel open probability (P(o)). We have identified S150 in the InsP(3)R2 core suppressor domain (amino acids 1-225) as the specific residue that is phosphorylated by CaMKII. Site-directed mutagenesis reveals that S150 is the CaMKII phosphorylation site responsible for modulation of channel activity. Nonphosphorylatable (S150A) and phosphomimetic (S150E) mutations were studied

SUBMITTER: Maxwell JT 

PROVIDER: S-EPMC3501088 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature