Overexpression of csk inhibits acid-induced activation of NHE-3

Yasuyoshi Yamaji, Morimasa Amemiya, Adriana Cano, Patricia A. Preisig, R. Tyler Miller, Orson W. Moe, Robert J. Alpern

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Opossum kidney OKP cells express an apical membrane Na+/H+ antiporter that is encoded by NHE-3 (for Na+/H+ exchanger 3) and is similar in many respects to the renal proximal tubule apical membrane Na+/H+ antiporter. Chronic incubation of OKP cells in acid medium for 24 hr increases Na+/H+- antiporter activity and NHE-3 mRNA abundance. The increase in Na+/H+- antiporter activity was not prevented by H7, a protein kinase C/protein kinase A inhibitor, but was prevented by herbimycin A, a tyrosine kinase inhibitor. Incubation of cells in acid medium increased c-src activity, and this was inhibited by herbimycin A. To determine the role of the src family of nonreceptor protein-tyrosine kinases, Csk for carboxyl-terminal src kinase), a physiologic inhibitor of these kinases, was overexpressed in OKP cells. In three clones overexpressing csk, acid-induced increases in Na+/H+-antiporter activity and NHE-3 mRNA abundance were inhibited. In these clones, inhibition of acid activation of Na+/H+-antiporter activity paralleled inhibition of acid activation of c-src. Neither herbimycin A nor overexpression of csk inhibited dexamethasone-induced increases in Na+/H+- antiporter activity. These studies show that decreases in pH activate c-src and that the src family nonreceptor protein-tyrosine kinases play a key role in acid activation of NHE-3.

Original languageEnglish (US)
Pages (from-to)6274-6278
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number14
DOIs
StatePublished - Jul 3 1995

Keywords

  • H antiporter
  • Na
  • acidosis
  • proximal tubule
  • src

ASJC Scopus subject areas

  • General

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