Phosphatidylinositol 4,5-bisphosphate stimulates protein kinase C-mediated phosphorylation of soluble brain proteins. Inhibition by neomycin.
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.
Chauhan
V P
VP
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D008970:Molecular Weight; D009355:Neomycin / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats
D004075:Diglycerides; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D009355:Neomycin; D002118:Calcium