The association of NHERF adaptor proteins with G protein-coupled receptors and receptor tyrosine kinases

The sodium-hydrogen exchanger regulatory factors (NHERF-1 and NHERF-2) are a family of adaptor proteins characterized by the presence of two tandem PDZ protein interaction domains and a C-terminal domain that binds the cytoskeleton proteins ezrin, radixin, moesin,and merlin. The NHERF proteins are highly expressed in the kidney, small intestine, and other organs, where they associate with a number of transporters and ion channels, signaling proteins, and transcription factors. Recent evidence has revealed important associations between the NHERF proteins and several G protein-coupled receptors such as the beta(2)-adrenergic receptor, the kappa-Opioid receptor, and the parathyroid hormone receptor, as well as growth factor tyrosine kinase receptors Such as the platelet-derived growth factor receptor and the epidermal growth factor receptor. This review summarizes the emerging data of e biochemical mechanisms, physiologic Outcomes, and potential clinical implications of the assembly and disassembly of receptor/NHERF complexes.