Assembly of signaling complexes by the sodium-hydrogen exchanger regulatory factor family of PDZ-containing proteins.
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.
Minkoff
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Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
Shenolikar
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Weinman
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D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
C505032:CFTR protein, human; D010750:Phosphoproteins; C000613385:SLC9A3 protein, human; C000613386:Slc9a3 protein, mouse; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019204:GTP-Binding Proteins