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

FEBS Lett. 1990 Oct 15;272(1-2):99-102. doi: 10.1016/0014-5793(90)80457-t.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium / metabolism
  • Cerebral Cortex / metabolism*
  • Diglycerides / pharmacology
  • Enzyme Activation / drug effects
  • Molecular Weight
  • Neomycin / pharmacology*
  • Nerve Tissue Proteins / metabolism*
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositols / pharmacology*
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Rats

Substances

  • Diglycerides
  • Nerve Tissue Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositols
  • Adenosine Triphosphate
  • Protein Kinase C
  • Neomycin
  • Calcium