THE RELATIONSHIP BETWEEN THE EFFECTS OF DRUGS ON BILAYER STABILITY AND ON PROTEIN-KINASE-C ACTIVITY

A variety of substances of diverse structure have been shown to affect the activity of protein kinase C. Many of the agents which affect protein kinase C activity also markedly shift the bilayer to hexagonal phase transition temperature of phosphatidylethanolamines. Although one of the more potent activators of protein kinase C, diacylglycerols, are effective destabilizers of the bilayer phase of membranes, this is not a general property of all protein kinase C activators nor are inhibitors of this enzyme bilayer stabilizing agents. However, if we consider only compounds which are unchanged or are zwitterionic, then those which promote the conversion of phospholipid bilayers to the hexagonal phase are all activators of protein kinase C, while those which stabilize the bilayer phase are protein kinase C inhibitors. Among charged substances, all of those which are negatively charged are activators of protein kinase C, while all of the positively charged compounds are protein kinase C inhibitors.