Modulation of brain polyphosphoinositide metabolism by acth-sensitive protein phosphorylation

Phosphorylation of membrane components is thought to be an important process in membrane function1. Phosphorylated proteins2 and a special class of phospholipids, the (poly)phos-phoinositides (poly PI)3, are implicated in the regulation of membrane permeability and synaptic transmission in neurones. For many years, protein phosphorylation and poly PI metabolism have been studied in parallel without knowledge of their possible interaction. We report here that the ACTH-sensitive protein kinase/B-50 protein complex which we recently isolated in soluble form from rat brain synaptosomal plasma membranes4,5 has lipid phosphorylating activity. Exogenously added phosphatidylinositol 4-phosphate (DPI) is phosphorylated to phosphatidylinositol 4,5-diphosphate (TPI), and this DPI-kinase activity is dependent on the state of phosphorylation of the protein kinase/B-50 protein complex. The results imply that phosphorylation of protein may affect the metabolism of (poly)PI in brain cell membranes