A new possible regulatory system for protein phosphorylation in human peripheral lymphocytes. II. Possible relation to phosphatidylinositol turnover induced by mitogens.
Ca++-activated, phospholipid-dependent protein kinase present in human peripheral lymphocytes requires a small amount of diacylglycerol in addition to phospholipid, particularly at lower concentrations of Ca++. It is necessary that such diacylglycerol contain unsaturated fatty acid at least at position 2. Saturated diacylglycerols such as dipalmitin and distearin are far less effective. Kinetic analysis indicates that unsaturated diacylglycerol greatly increases the apparent affinity of the enzyme for phospholipid, and sharply decreases the Ca++ concentration to the micromolar range that gives rise to the maximum enzyme activation. Among various phospholipids tested, phosphatidylserine is most active in supporting enzymatic activity. Phosphatidylinositol and phosphatidylethanolamine are less effective. Phosphatidylcholine, phosphatidic acid, sphingomyelin, and lysophosphatidylcholine are inert. It is most likely, therefore, that various lymphocyte mitogens induce specific hydrolysis of phosphatidylinositol to produce such an active unsaturated diacylglycerol, which in turn serves as a second messenger for the selective activation of this unique protein kinase. Dibucaine and chlorpromazine appear to interact with phospholipid and thereby inhibit the activation process of this enzyme. Cyclic nucleotide-dependent protein kinases are not susceptible to these phospholipid-interacting drugs.
D002746:Chlorpromazine / Q000494:pharmacology; D003992:Dibucaine / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000494:pharmacology; D008214:Lymphocytes / Q000201:enzymology*; D008934:Mitogens / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000494:pharmacology; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*
D004075:Diglycerides; D008055:Lipids; D008934:Mitogens; D010716:Phosphatidylinositols; D010743:Phospholipids; D011494:Protein Kinases; D003992:Dibucaine; D002746:Chlorpromazine