Activation of calcium and phospholipid-dependent protein kinase by diacylglycerol, its possible relation to phosphatidylinositol turnover.
Ca2+-activated, phospholipid-dependent protein kinase from various mammalian tissues (Takai, Y., Kishimoto, A., Iwasa, Y., Kawahara, Y., Mori, T., and Nishizuka, Y (1979) J. Biol. Chem. 254, 3692-3695) was greatly stimulated by the addition of diacylglycerol at less than 5% (w/w) the concentration of phospholipid. This stimulation was due to an increase in the apparent affinity of enzyme for phospholipid and to a concomitant decrease in the Ka value for Ca2+ from about 1 x 10(-4) M to the micromolar range. Diacylglycerol alone showed little or no effect on enzymatic activity over a wide range of Ca2+ concentrations. This effect was greatest for diacylglycerol which contained unsaturated fatty acid at least at position 2. The active diacylglycerols so far tested included diolein, dilinolein, diarachidonin, 1-stearoyl-2-oleoyl diglyceride, and 1-stearoyl-2-linoleoyl diglyceride. In contrast, diacylglycerols containing saturated fatty acids such as dipalmitin and distearin were far less effective. Triacyl- and monoacylglycerols were totally ineffective, irrespective of the fatty acyl moieties. Cholesterol and free fatty acids were also ineffective. Based on these observations, a possible coupling is proposed between the protein kinase activation and phosphatidylinositol turnover which can be provoked by various extracellular messengers.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation; D005989:Glycerides / Q000494:pharmacology*; D007700:Kinetics; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats
D004075:Diglycerides; D005989:Glycerides; D010716:Phosphatidylinositols; D010743:Phospholipids; D011494:Protein Kinases; D002118:Calcium