Phosphatidylinositol 4,5-bisphosphate stimulates protein kinase C-mediated phosphorylation of soluble brain proteins. Inhibition by neomycin

Abstract

Phosphatidylinositol 4,5-bisphosphate (PIP2) at 0.1 mol% activated the protein kinase C (PKC)-mediated phosphorylation of 87-, 55- and 47-kDa brain proteins. Neomycin, an aminoglycoside antibiotic that binds PIP2 with a high affinity, inhibited PIP2.PKC activity in a concentration-dependent manner. Low concentrations of neomycin (less than 2 mM) did not affect DG.PKC activity; however, 4 mM neomycin inhibited 50% of this activity. This inhibition of DG-stimulated activity at high neomycin concentration may be the result of its binding to Ca2+ and ATP in the assay system. These results suggest that PIP2 is a physiological activator of PKC, and show that neomycin can be an inhibitor of PIP2.PKC activity at concentrations where DG.PKC activity is not affected.