Protein kinase C activity in pancreatic islets: effects of Ca2+, calmodulin and retinoic acid

Pancreatic islet homogenates display protein kinase C activity. Although the rate of histone phosphorylation by islet homogenates is not enhanced by Ca2+ alone, the Ca2+ ion markedly augments reaction velocity in the presence of phosphatidylserine and at low concentrations (20 nM--0.2 microM) of the tumor-promoting agent 12-0-tetradecanoylphorbol-13-acetate (TPA). At a higher concentration (2.0 microM), TPA stimulates histone phosphorylation even in the absence of Ca2+. Ca-calmodulin also stimulates protein phosphorylation but the latter effect is apparently mediated by a Ca-calmodulin-responsive protein kinase distinct from the protein kinase C. In the presence of phosphatidylserine, retinoic acid (0.1 microM) fails to cause any obvious change in protein kinase C activity. However, in the 0.1-100.0 microM range, retinoic acid confers a limited responsiveness to TPA in the absence of phosphatidylserine. These findings support the view that Ca2+ may regulate protein phosphorylation in the pancreatic B-cell through several distinct pathways.