Role of tyrosine kinase pathways in ET(B) receptor activation of NHE3

Tzong Shinn Chu, Hirohiko Tsuganezawa, Yan Peng, Adriana Cano, Masashi Yanagisawa, Robert J. Alpern

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Endothelin-1 (ET-1) binding to ET(B) receptors increases the activity of the apical membrane Na+/H+ antiporter (NHE3) of renal proximal tubule and cultured OKP cells. In OKPET(B)6 cells, a clonal cell line of OKP cells that overexpresses ET(B) receptors, ET-1-induced increases in Na+/H+ antiporter activity are mediated 50% by Ca2+dependent pathways and 50% by tyrosine kinase pathways. ET-1 induces tyrosine phosphorylation of proteins of 68, 110, 125, 130, and 210 kDa. ET-1-induced tyrosine phosphorylation is mediated by the ET(B) receptor and is not dependent on increases in cell Ca2+ or protein kinase C. The 68-, 110-, 125-, and 130-kDa phosphoproteins are cytosolic, whereas the 210-kDa phosphoprotein is an integral membrane protein. Immunoprecipitation studies showed that the 68-kDa protein is paxillin and the 125-kDa protein is p125(FAK) (focal adhesion kinase). Cytochalasin D, which disrupts focal adhesions, prevented ET-1-induced tyrosine phosphorylation of paxillin, p110, p125(FAK), and p130 but did not prevent tyrosine phosphorylation of p210 and did not prevent ET-1-induced increases in Na+/H+ antiporter activity. Thus 50% of ET(B) receptor- induced Na+/H+ antiporter activation is mediated by tyrosine kinase pathways, possibly involving p210. ET(B) receptor activation also induces tyrosine phosphorylation of focal adhesion proteins, but this is not required for antiporter activation.

Original languageEnglish (US)
Pages (from-to)C763-C771
JournalAmerican Journal of Physiology - Cell Physiology
Issue number3 40-3
StatePublished - Sep 1996


  • endothelin receptors
  • focal adhesion kinase
  • focal adhesions
  • p130
  • paxillin
  • sodium/hydrogen antiporter

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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