The plasma membrane H+-ATPase from the yeast Saccharomyces cerevisiae is a proton pump that plays an essential role in the yeast phisiology. The activity of this enzyme is regulated at both transcriptional and post-translational levels and a remarkable characteristic is the fact that it is activated by glucose, low pH and depolarizing agents. The H+-ATPase activation pathway by depolarizing agents is still unknown. In this work we suggest that a phosphatidylinositol type signaling pathway is involved in the H+-ATPase activation by carbolnyl cyanide n-chlorophenylhydrazone. In this pathway this compound would activate the enzyme phosphplipase C that would promote the hydrolysis of the phosphatidylinositol biphosphate in two components, diacylglycerol and inositol tri-phosphate. The inositol triphosphate generated would promote the calcium mobilization. The increase in the levels of cytosolic calcium together with the diacylglycerol formation could trigger the activation of the protein kinase C, that once activated would be phosphorylate the H+-ATPase turning it activated. Furthermore, we measured the additive effect of glucose in the ATPase activated by CCCP. The results indicated that the ATPase activation by glucose may be triggered by two different branches from a unique pathway: one also activated by CCCP and other specific for sugars as suggested by Tropia et al., 2006. Biochem. Biophys. Res. Comm. (in press).