Long-chain fatty acyl-coenzyme A's activate both the ligand-binding and protein kinase activities of phorboid and ingenoid receptor

Abstract

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 (C 10C 2), like certain acidic phospholipids, activated the ligand-receptor interaction. The extent of activation increased with the increasing chain length of fatty acyl-CoA. Shortchain fatty acyl-CoAs (C 0C 6), 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 (C 10-C 20) and SDS in a dose-dependent manner. K m values for ATP and protein substrate were the same in the absence and presence of stearoyl-CoA; however, V max 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.