Long-chain fatty acyl-coenzyme A's activate both the ligand-binding and protein kinase activities of phorboid and ingenoid receptor.
Modulation of the ligand-binding activity and protein kinase activity of homogeneous phorboid and ingenoid receptor from the brain by various fatty acyl-CoAs, fatty acid esters, fatty acids, and detergents was studied. Long-chain fatty acyl-CoAs (C10-C20), like certain acidic phospholipids, activated the ligand-receptor interaction. The extent of activation increased with the increasing chain length of fatty acyl-CoA. Short-chain fatty acyl-CoAs (C0-C6), fatty acids, and fatty acid esters were essentially inactive. Sodium dodecyl sulfate (SDS) also activated the ligand binding, but other detergents (Triton X-100, deoxycholic acid, Nonidet-40, and Tween-80) were ineffective. The combination of phosphatidylserine and stearoyl-CoA was as effective as each agent alone in the activation of ligand-receptor interaction, suggesting similar mechanisms of action. The basal protein kinase activity of phorboid receptor was stimulated by long-chain fatty acyl-CoAs (C10-C20) and SDS in a dose-dependent manner. Km values for ATP and protein substrate were the same in the absence and presence of stearoyl-CoA; however, Vmax was increased in the presence of the active agents. The degree of stimulation of protein kinase activity by stearoyl-CoA was independent of receptor protein concentration. Stearoyl-CoA did not significantly influence the activity of the catalytic subunit of cyclic AMP-dependent protein kinase. The combined hydrophobic and acidic nature of the active agents appears to be important in activating both the ligand-binding and protein kinase activities of phorboid receptor.
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003902:Detergents / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology
D000214:Acyl Coenzyme A; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003902:Detergents; D008024:Ligands; D010703:Phorbol Esters; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C027777:ingenol ester receptor; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C017725:stearoyl-coenzyme A; D012967:Sodium Dodecyl Sulfate; D015240:Phorbol 12,13-Dibutyrate; D011494:Protein Kinases; D011493:Protein Kinase C