Intracellular acidosis activates c-Src

Yasuyoshi Yamaji, Hirohiko Tsuganezawa, Orson W. Moe, Robert J. Alpern

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

The purpose of the present studies was to determine whether acidosis activates protein tyrosine kinase pathways. Incubation of MCT cells, a renal proximal tubule cell line, in acid media caused increased phosphotyrosine content of 60- to 70- and 120-kDa cytosolic proteins. Media acidification induced a twofold increase in c-Src activity that occurred 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 addition, maneuvers that decrease intracellular pH in the absence of changes in extracellular pH, activated c- Src. Significant activation by sodium propionate was seen with cell pH changes as small as 0.07 pH unit. Sodium orthovanadate, a protein tyrosine phosphatase inhibitor, prevented c-Src activation by media acidification but did not prevent protein tyrosine phosphorylation. In summary, decreased intracellular pH activates c-Src. Acid activation of c-Src represents a novel mechanism of c-Src activation that may be relevant to many cellular responses to acidosis.

Original languageEnglish (US)
Pages (from-to)C886-C893
JournalAmerican Journal of Physiology - Cell Physiology
Volume272
Issue number3 41-3
DOIs
StatePublished - Mar 1997

Keywords

  • MCT cells
  • proximal tubule
  • tyrosine phosphorylation
  • vanadate

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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