Regulation of protein kinase C activity by gangliosides.
The activity of protein kinase C (Ca2+/phospholipid-dependent enzyme) in the presence of phosphatidylserine and its physiological regulator, diacylglycerol, could be suppressed by a mixture of brain gangliosides. Half-maximal inhibition was observed at 30 microM and was nearly complete at 100 microM. Inhibition was observed at all concentrations of Ca2+ between 10(-8) and 10(-4) M. Inhibition of protein kinase C activity could not be reversed by increasing the concentration of diacylglycerol or the substrate, histone. Inhibition was also observed when myelin basic protein or a synthetic myelin basic protein peptide was used as substrate. Among the individual gangliosides, the rank order of potency was GT1b greater than GD1a = GD1b greater than GM3 = GM1. Our results suggest that gangliosides may regulate the responsiveness of protein kinase C to diacylglycerol.
D000818:Animals; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D004075:Diglycerides / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005732:Gangliosides / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004075:Diglycerides; D005732:Gangliosides; D006657:Histones; D004676:Myelin Basic Protein; D010718:Phosphatidylserines; D011493:Protein Kinase C; D002118:Calcium; C013965:diolein