INTRACELLULAR ACIDOSIS ACTIVATES C-SRC

The purpose of the present studies was to determine whether acidosis a ctivates protein tyrosine kinase pathways. Incubation of MCT cells, a renal proximal tubule cell line, in acid media caused increased phosph otyrosine content of 60- to 70- and 120-kDa cytosolic proteins. Media acidification induced a twofold increase in c-Src activity that occurr ed within 30 s. Significant activation occurred with media pH changes as small as 0.07 pH unit accompanied by cell acidification of 0.06 pH unit. Sodium propionate addition, NH4Cl prepulse, and nigericin additi on, maneuvers that decrease intracellular pH in the absence of changes in extracellular pH, activated c-Src. Significant activation by sodiu m propionate was seen with cell pH changes as small as 0.07 pH unit. S odium orthovanadate, a protein tyrosine phosphatase inhibitor, prevent ed c-Src activation by media acidification but did not prevent protein tyrosine phosphorylation. In summary, decreased intracellular pH acti vates c-Src. Acid activation of c-Src represents a novel mechanism of c-Src activation that may be relevant to many cellular responses to ac idosis.