Stimulation of nuclear protein kinase C leads to phosphorylation of nuclear inositol 1,4,5-trisphosphate receptor and accelerated calcium release by inositol 1,4,5-trisphosphate from isolated rat liver nuclei.
Rat liver nuclei inositol 1,4,5-trisphosphate receptor (Malviya, A.N., Rogue, P., and Vincendon, G. (1990) Proc. Natl. Acad. Sci U.S.A. 87, 9270-9274) is identified as a 220-kDa protein on Western blotting employing two types of antibodies (anti-goat and anti-rabbit) raised against purified rat brain inositol 1,4,5-trisphosphate receptor (IP3R). Nuclear IP3R does not seem identical with microsomal IP3R in rat liver. Treatment of isolated rat liver nuclei with 12-O-tetradecanoylphorbol-13-acetate stimulates native protein kinase C activity severalfold. Nuclear IP3R is phosphorylated by stimulated protein kinase C, with accelerated as well as enhanced maximum 45Ca2+ release by inositol 1,4,5-trisphosphate from isolated nuclei, without altering 1,4,5-trisphosphate binding characteristics (KD and Bmax). Stimulation of nuclear protein kinase C is found physiologically relevant since lamin B2, a nuclear protein, is concomitantly phosphorylated. These data deal with functional consequences of nuclear IP3R phosphorylation by native protein kinase C in isolated rat liver nuclei. It is postulated that phosphorylation of nuclear IP3R, probably dephosphorylation also, subserves a key mechanism in nuclear calcium homeostasis.
Laboratoire de Neurobiologie Moléculaire des Interactions Cellulaire, Centre National de la Recherche Scientifique, Strasbourg, France.
N
N
Matter
M F
MF
Ritz
S
S
Freyermuth
P
P
Rogue
A N
AN
Malviya
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism* / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D034921:Lamin Type B; D034882:Lamins; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium