Possible Involvement of a Phosphatidylinositol-Type Signaling Pathway in Glucose-Induced Activation of Plasma Membrane H(+)-ATPase and Cellular Proton Extrusion in the Yeast Saccharomyces Cerevisiae

Biochim Biophys Acta. 1994 Aug 11;1223(1):117-24. doi: 10.1016/0167-4889(94)90080-9.


Addition of glucose to cells of the yeast Saccharomyces cerevisiae causes rapid activation of plasma membrane H(+)-ATPase and a stimulation of cellular H+ extrusion. We show that addition of diacylglycerol and other activators of protein kinase C to intact cells also activates the H(+)-ATPase and causes at the same time a stimulation of H+ extrusion from the cells. Both effects are reversed by addition of staurosporine, a protein kinase C inhibitor. Addition of staurosporine or calmidazolium, an inhibitor of Ca2+/calmodulin-dependent protein kinases, separately, causes a partial inhibition of glucose-induced H(+)-ATPase activation and stimulation of cellular H+ extrusion; together they cause a more potent inhibition. Addition of neomycin, which complexes with phosphatidylinositol 4,5-bisphosphate, or addition of compound 48/80, a phospholipase C inhibitor, also causes near complete inhibition. Diacylglycerol and other protein kinase C activators had no effect on the activity of the K(+)-uptake system and the activity of trehalase and glucose-induced activation of the K(+)-uptake system and trehalase was not inhibited by neomycin, supporting the specificity of the effects observed on the H(+)-ATPase. The results support a model in which glucose-induced activation of H(+)-ATPase is mediated by a phosphatidylinositol-type signaling pathway triggering phosphorylation of the enzyme both by protein kinase C and one or more Ca2+/calmodulin-dependent protein kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Cell Membrane / enzymology
  • Diglycerides / pharmacology
  • Enzyme Activation / drug effects
  • Glucose / pharmacology*
  • Imidazoles / pharmacology
  • Phosphatidylinositols / metabolism*
  • Phosphorylation
  • Proton-Translocating ATPases / antagonists & inhibitors
  • Proton-Translocating ATPases / metabolism*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / ultrastructure
  • Signal Transduction
  • Staurosporine
  • p-Methoxy-N-methylphenethylamine / pharmacology


  • Alkaloids
  • Diglycerides
  • Imidazoles
  • Phosphatidylinositols
  • 1,2-dioctanoylglycerol
  • p-Methoxy-N-methylphenethylamine
  • calmidazolium
  • Proton-Translocating ATPases
  • Staurosporine
  • Glucose