title: Regulation of the phosphorylation of the inositol 1,4,5-trisphosphate receptor by protein kinase C.
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.
authors.affiliation: Laboratory of Physiology, K.U. Leuven Campus Gasthuisberg O/N, B-3000 Leuven, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Vermassen
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Fissore
authors.forename: Nael
authors.initials: N
authors.lastname: Nadif Kasri
authors.forename: Veerle
authors.initials: V
authors.lastname: Vanderheyden
authors.forename: Geert
authors.initials: G
authors.lastname: Callewaert
authors.forename: Ludwig
authors.initials: L
authors.lastname: Missiaen
authors.forename: Jan B
authors.initials: JB
authors.lastname: Parys
authors.forename: Humbert
authors.initials: H
authors.lastname: De Smedt
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D002147:Calmodulin; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium