MOLECULAR PHARMACOLOGY, 43:286-292 Regulation of Phosphatidylinositol 4-Kinase Activity

Previous data showed that carbachol (CCh) elicits a concentra-tion-dependent increase in phosphatidylinositol (Ptdlns) 4-kinase activity in homogenates derived from agonist-stimulated pan-creatic acini. In the present study CCh elicited a time-dependent increase in Ptdlns 4-kinase activity, which was blocked by n-methylscopolamine and mimicked by muscarine. A membrane-associated Ptdlns 4-kinase activity was identified that displayed maximal activity in the pH range of5.5-8.5. The zymogen granule fraction possessed relatively high specific enzyme activity, which was sensitive to CCIi stimulation. The enzyme had apparent Km values for Ptdlns and ATP of 4 and 60 taM, respectively. CCh caused no discernible change in the Km for either Ptdlns or ATP but increased V. Dioctanoylglycerol and oleoyl acetylglycerol augmented Ptdlns 4-kinase activity, which was blocked by stau-rosporine, thus suggesting a possible role for protein kinase