Assembly of signaling complexes by the sodium-hydrogen exchanger regulatory factor family of PDZ-containing proteins.

Journal Article (Journal Article;Review)

The sodium-hydrogen exchanger regulatory factor (NHERF) was first identified as an essential cofactor for cyclic AMP-mediated inhibition of the epithelial isoform of rabbit kidney sodium-hydrogen exchanger (NHE3). More recent work shows that NHERF constitutes a family of PSD-95/DIg/ZO-1 (PDZ) domain-containing adapter proteins, only some of which associate with the NHE3 antiporter. Other targets of the NHERF proteins include members of the ezrin-radixin-moesin family of cytoskeletal proteins. In the current model for NHE3 regulation, NHERF links NHE3 to the protein kinase A-anchoring protein, ezrin, and thereby facilitates its phosphorylation and inhibition by protein kinase A. Recent studies have also established the interaction of NHERF and its homologs with the beta2-adrenergic receptor and the platelet-derived growth factor receptor tyrosine kinase that facilitates signal transduction by these receptors. Association with NHERF may also regulate the cystic fibrosis transmembrane conductance regulator and the sodium-bicarbonate transporter. With the rapid increase in the intracellular targets identified for NHERF, the emerging data point to a broad role for these PDZ-containing proteins in the organization of signaling complexes and control of cell physiology.

Full Text

Duke Authors

Cited Authors

  • Minkoff, C; Shenolikar, S; Weinman, EJ

Published Date

  • September 1999

Published In

Volume / Issue

  • 8 / 5

Start / End Page

  • 603 - 608

PubMed ID

  • 10541224

International Standard Serial Number (ISSN)

  • 1062-4821

Digital Object Identifier (DOI)

  • 10.1097/00041552-199909000-00012


  • eng

Conference Location

  • England