NHE3 regulatory factor 1 (NHERF-1) is a multifunctional adaptor protein that interacts with NHE3 via its PDZ domains. The amino-terminal PDZ domain regulates the dimerization of NHERF-1 in vivo. G protein-coupled receptor kinase 6A phosphorylates NHERF-1 at Ser 289 via a PDZ domain-mediated interaction.