Acute regulation of Na/H exchanger NHE3 activity by protein kinase C: Role of NHE3 phosphorylation

Michael R. Wiederkehr, Hui Zhao, Orson W. Moe

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Acute hormonal modulation of NHE3 activity is partly mediated by kinases, including protein kinase C (PKC). We examined the role of NHE3 phosphorylation in regulating its activity in response to PKC activation by phorbol 12-myristate 13-acetate (PMA). In pooled NHE-deficient fibroblasts transfected with NHE3, PMA increased NHE3 activity and phosphorylation. When six potential PKC target serines were mutated, NHE3 phosphorylation was drastically reduced and PMA failed to regulate NHE3 phosphorylation or function. To examine whether NHE3 phosphorylation is sufficient for functional regulation by PKC, we exploited the heterogeneous response of NHE3 activity to PMA in individual clones of transfectants. Clones with stimulatory, inhibitory, or null responses to PMA were observed. Despite the diverse functional response, changes in NHE3 phosphorylation as revealed by tryptic phosphopeptide maps were similar in all clones. We conclude that although phosphorylation appears to be necessary, it is insufficient to mediate PKC regulation of NHE3 function and factors extrinsic to the NHE3 protein must be involved.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number5 45-5
StatePublished - 1999

Fingerprint

Sodium-Hydrogen Antiporter
Phosphorylation
Protein Kinase C
Acetates
Clone Cells
Phosphopeptides
Fibroblasts
Serine
Phosphotransferases
Chemical activation
Modulation
phorbol-12-myristate

Keywords

  • Hormones
  • Proximal tubule
  • Sodium bicarbonate transport
  • Sodium chloride transport

ASJC Scopus subject areas

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

Cite this

Acute regulation of Na/H exchanger NHE3 activity by protein kinase C : Role of NHE3 phosphorylation. / Wiederkehr, Michael R.; Zhao, Hui; Moe, Orson W.

In: American Journal of Physiology - Cell Physiology, Vol. 276, No. 5 45-5, 1999.

Research output: Contribution to journalArticle

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