Phospholipase Cbeta2 binds to and inhibits phospholipase Cdelta1.
Phospholipase Cbeta (PLCbeta) isoforms, which are under the control of Galphaq and Gbetagamma subunits, generate Ca2+ signals induced by a broad array of extracellular agonists, whereas PLCdelta isoforms depend on a rise in cytosolic Ca2+ for their activation. Here we find that PLCbeta2 binds strongly to PLCdelta1 and inhibits its catalytic activity in vitro and in living cells. In vitro, this PLC complex can be disrupted by increasing concentrations of free Gbetagamma subunits. Such competition has consequences for signaling, because in HEK293 cells PLCbeta2 suppresses elevated basal [Ca2+] and inositol phosphates levels and the sustained agonist-induced elevation of Ca2+ levels caused by PLCdelta1. Also, expression of both PLCs results in a synergistic release of [Ca2+] upon stimulation in A10 cells. These results support a model in which PLCbeta2 suppresses the basal catalytic activity of PLCdelta1, which is relieved by binding of Gbetagamma subunits to PLCbeta2 allowing for amplified calcium signals.
Guo
Yuanjian
Y
Department of Physiology and Biophysics, State University of New York, Stony Brook, New York 11794-8661, USA.
Rebecchi
Mario
M
Scarlata
Suzanne
S
D000109:Acetylcholine / Q000494:pharmacology; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002384:Catalysis; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D005453:Fluorescence; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D054799:Phospholipase C beta; D054803:Phospholipase C delta; D011485:Protein Binding / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D007295:Inositol Phosphates; D007527:Isoenzymes; D010738:Type C Phospholipases; C518024:PLCD1 protein, human; D054799:Phospholipase C beta; D054803:Phospholipase C delta; D020962:Heterotrimeric GTP-Binding Proteins; D000109:Acetylcholine; D002118:Calcium