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 identifie d as an essential cofactor for cyclic AMP-mediated inhibition of the epithe lial 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 an tiporter, Other targets of the NHERF proteins include members of the ezrin- radixin-moesin family of cytoskeletal proteins, In the current model for NH E3 regulation, NHERF links NHE3 to the protein kinase A-anchoring protein, ezrin, and thereby facilitates its phosphorylation and inhibition by protei n kinase A, Recent studies have also established the interaction of NHERF a nd its homologs with the Bz-adrenergic receptor and the platelet-derived gr owth factor receptor tyrosine kinase that facilitates signal transduction b y these receptors, Association with NHERF may also regulate the cystic fibr osis transmembrane conductance regulator and the sodium-bicarbonate transpo rter, With the rapid increase in the intracellular targets identified for N HERF, the emerging data point to a broad role for these PDZ-containing prot eins in the organization of signaling complexes and control of cell physiol ogy. Curr Opin Nephrol Hypertens 8:603-608. (C) 1999 Lippincott Williams & Wilkins.