Regulation of the Atrial Natriuretic Peptide Receptor Guanylyl Cyclase

The discovery of atrial natriuretic peptide (ANP) and the demonstration that its receptors were coupled to the activation of particulpate guanylyl cyclase (GC) and that ANP receptors copurified with GC activity were important findings in the 1980s. With the molecular cloning of the ANP receptor, the knowledge gained of its structure has allowed new questions to be posed about how signaling through this receptor is regulated-and about signaling through a growing family of related receptors having intrinsic GC activity (1). Here, I review experiments addressing the role of the protein kinase-like domain of the ANP receptor, the regulation of receptor function by adenine nucleotides, the role of dimerization in receptor activation, and the identification of a novel protein-serine phos-phatase that may mediate desensitization of the ANP receptor.