ET(B) receptor activation leads to activation and phosphorylation of NHE3

Yan Peng, Orson W Moe, T. S. Chu, P. A. Preisig, Masashi Yanagisawa, R. J. Alpern

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

In OKP cells expressing ET(B) endothelin receptors, activation of Na +/H + antiporter activity by endothelin-1 (ET-1) was resistant to low concentrations of ethylisopropyl amiloride, indicating regulation of Na +/H + exchanger isoform 3 (NHE3). ET-1 increased NHE3 phosphorylation in cells expressing ET(B) receptors but not in cells expressing ET(A) receptors. Receptor specificity was not due to demonstrable differences in receptor- specific activation of tyrosine phosphorylation pathways or inhibition of adenylyl cyclase. Phosphorylation was associated with a decrease in mobility on SDS-PAGE, which was reversed by treating immunoprecipitated NHE3 with alkaline phosphatase. Phosphorylation was first seen at 5 min and was maximal at 15-30 min. Phosphorylation was maximal with 10 -9 M ET-1. Phosphorylation occurred on threonine and serine residues at multiple sites. In summary, ET- 1 induces NHE3 phosphorylation in OKP cells on multiple threonine and serine residues. ET(B) receptor specificity, time course, and concentration dependence are all similar between ET-1-induced increases in NHE3 activity and phosphorylation, suggesting that phosphorylation plays a key role in activation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number4 45-4
StatePublished - 1999

Fingerprint

Sodium-Hydrogen Antiporter
Phosphorylation
Protein Isoforms
Chemical activation
Endothelin-1
Cells
Threonine
Serine
Endothelin B Receptors
Amiloride
Adenylyl Cyclases
Alkaline Phosphatase
Tyrosine
Polyacrylamide Gel Electrophoresis

Keywords

  • Adenylyl cyclase
  • Endothelin
  • OKP cells
  • Sodium/hydrogen antiporter
  • Tyrosine kinases

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

ET(B) receptor activation leads to activation and phosphorylation of NHE3. / Peng, Yan; Moe, Orson W; Chu, T. S.; Preisig, P. A.; Yanagisawa, Masashi; Alpern, R. J.

In: American Journal of Physiology - Cell Physiology, Vol. 276, No. 4 45-4, 1999.

Research output: Contribution to journalArticle

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AU - Peng, Yan

AU - Moe, Orson W

AU - Chu, T. S.

AU - Preisig, P. A.

AU - Yanagisawa, Masashi

AU - Alpern, R. J.

PY - 1999

Y1 - 1999

N2 - In OKP cells expressing ET(B) endothelin receptors, activation of Na +/H + antiporter activity by endothelin-1 (ET-1) was resistant to low concentrations of ethylisopropyl amiloride, indicating regulation of Na +/H + exchanger isoform 3 (NHE3). ET-1 increased NHE3 phosphorylation in cells expressing ET(B) receptors but not in cells expressing ET(A) receptors. Receptor specificity was not due to demonstrable differences in receptor- specific activation of tyrosine phosphorylation pathways or inhibition of adenylyl cyclase. Phosphorylation was associated with a decrease in mobility on SDS-PAGE, which was reversed by treating immunoprecipitated NHE3 with alkaline phosphatase. Phosphorylation was first seen at 5 min and was maximal at 15-30 min. Phosphorylation was maximal with 10 -9 M ET-1. Phosphorylation occurred on threonine and serine residues at multiple sites. In summary, ET- 1 induces NHE3 phosphorylation in OKP cells on multiple threonine and serine residues. ET(B) receptor specificity, time course, and concentration dependence are all similar between ET-1-induced increases in NHE3 activity and phosphorylation, suggesting that phosphorylation plays a key role in activation.

AB - In OKP cells expressing ET(B) endothelin receptors, activation of Na +/H + antiporter activity by endothelin-1 (ET-1) was resistant to low concentrations of ethylisopropyl amiloride, indicating regulation of Na +/H + exchanger isoform 3 (NHE3). ET-1 increased NHE3 phosphorylation in cells expressing ET(B) receptors but not in cells expressing ET(A) receptors. Receptor specificity was not due to demonstrable differences in receptor- specific activation of tyrosine phosphorylation pathways or inhibition of adenylyl cyclase. Phosphorylation was associated with a decrease in mobility on SDS-PAGE, which was reversed by treating immunoprecipitated NHE3 with alkaline phosphatase. Phosphorylation was first seen at 5 min and was maximal at 15-30 min. Phosphorylation was maximal with 10 -9 M ET-1. Phosphorylation occurred on threonine and serine residues at multiple sites. In summary, ET- 1 induces NHE3 phosphorylation in OKP cells on multiple threonine and serine residues. ET(B) receptor specificity, time course, and concentration dependence are all similar between ET-1-induced increases in NHE3 activity and phosphorylation, suggesting that phosphorylation plays a key role in activation.

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