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 Bz-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. Curr Opin Nephrol Hypertens 8:603-608. (C) 1999 Lippincott Williams & Wilkins.