Phosphatidylinositol4,Sbisphosphate stimulates protein kinase C-mediated phosphorylation of soluble Inhibition by neomycin

Phosphatidylinositol4,5-bisphosphate (PIP,) at 0.1 mob% activated the protein kinase C (PKC)-mediated phosphorylation of 87-, 55and 47-kDa brain proteins. Neomycin, an aminoglycoside antibiotic that binds PIP, with a high affinity, inhibited PIP;PKC activity in a concentration-dependent manner. Low concentrations of neomycin (< 2 mM) did not affect DG.PKC activity; however, 4 mM neomycin inhibited SW of this activity. This inhibition of DG-stimulated activity at high neomycin concentration may be the result of its binding to Ca*+ and ATP in the assay system. These results suggest that PIP, is a physiological activator of PKC, and show that neomycin can be an inhibitor of PIP,.PKC activity at concentrations where DG.PKC activity is not affected.