Regulation of the phosphorylation of the inositol 1,4,5-trisphosphate receptor by protein kinase C

Biochem Biophys Res Commun. 2004 Jul 2;319(3):888-93. doi: 10.1016/j.bbrc.2004.05.071.

Abstract

The various inositol 1,4,5-trisphosphate receptor (IP(3)R) isoforms are potential substrates for several protein kinases. We compared the in vitro phosphorylation of purified IP(3)R1 and IP(3)R3 by the catalytic subunit of protein kinase C (PKC). Phosphorylation of IP(3)R1 by PKC was about eight times stronger than that of IP(3)R3 under identical conditions. Protein kinase A strongly stimulated the PKC-induced phosphorylation of IP(3)R1. In contrast, Ca(2+) inhibited its phosphorylation (IC(50)<or=2microM) and this inhibition was further potentiated by calmodulin (CaM), while the Ca(2+)-independent CaM mutant CaM(1234) was ineffective. Ca(2+) and CaM, however, did not inhibit IP(3)R3 phosphorylation by PKC. Taken together, these findings show that Ca(2+) and CaM differentially regulate the PKC-mediated phosphorylation of IP(3)R1 and IP(3)R3 and are indicative for a role for the inhibition of IP(3)R1 phosphorylation by Ca(2+) and CaM in the negative slope of the bell-shaped effect of Ca(2+) on IP(3)R function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Calmodulin / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors
  • Mice
  • Phosphorylation
  • Protein Isoforms / metabolism
  • Protein Kinase C / metabolism*
  • Rats
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Calcium Channels
  • Calmodulin
  • Inositol 1,4,5-Trisphosphate Receptors
  • Protein Isoforms
  • Receptors, Cytoplasmic and Nuclear
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Calcium