Regulation of the phosphorylation of the inositol 1,4,5-trisphosphate receptor by protein kinase C.
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.
Vermassen
Elke
E
Laboratory of Physiology, K.U. Leuven Campus Gasthuisberg O/N, B-3000 Leuven, Belgium.
Fissore
Rafael A
RA
Nadif Kasri
Nael
N
Vanderheyden
Veerle
V
Callewaert
Geert
G
Missiaen
Ludwig
L
Parys
Jan B
JB
De Smedt
Humbert
H
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*
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