G-protein betagamma subunits antagonize protein kinase C-dependent phosphorylation and inhibition of phospholipase C-beta1.
Protein kinase C (PKC) isoforms phosphorylated phospholipase C-beta1 (PLC-beta1) in vitro as follows: PKCalpha >> PKCepsilon; not PKCzeta. PLC-beta3 was not phosphorylated by PKCalpha. G-protein betagamma subunits inhibited the PKCalpha phosphorylation of PLC-beta1 in a concentration-dependent manner. Half-maximal inhibition occurred with 500 nM betagamma. G-protein betagamma subunits also antagonized the PKCalpha-mediated inhibition of PLC-beta1 enzymic activity. PKCalpha, in turn, inhibited the stimulation of PLC-beta1 activity by betagamma. There was little effect of PKCalpha on the stimulation of PLC-beta1 by alphaq/11-guanosine 5'[gamma-thio]triphosphate (GTP[S]). These findings demonstrate that G protein betagamma subunits antagonize PKCalpha regulation of PLC-beta1. Thus betagamma subunits might have a role in modulating the negative feedback regulation of this signalling system by PKC.
Litosch
I
I
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL 33101, USA.
D000818:Animals; D002417:Cattle; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D054799:Phospholipase C beta; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*
D007527:Isoenzymes; D011493:Protein Kinase C; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins