Cloning of Guonylyl Cyclase Isoforms

Publisher Summary This chapter describes the cDNA cloning and expression studies for particulate and soluble guanylyl cyclases that have taken place in several laboratories. The synthesis of cyclic GMP is catalyzed by guanylyl cyclase [GTP pyrophosphate-lyase (cyclizing)] and the enzyme is present in several particulate and soluble isoforms, which are structurally different proteins with different properties. The particulate isoforms can be activated by natriuretic peptides and Escherichia coli heat-stable enterotoxin, whereas the soluble enzyme can be activated by nitric oxide and some porphyrins. Recently, the structures of some particulate and soluble guanylyl cyclases have been described from various sources and an activation mechanism has been proposed. The human particulate guanylyl cyclase cDNA has been used as a probe to isolate a cDNA coding for particulate guanylyl cyclase from a rat brain cDNA library. The deduced sequence of the atrial natriuretic peptide (ANP) receptor/guanylyl cyclase is consistent with the notion that the ANP-binding portion is on the exterior surface and the homologous region to the protein-kinase family and the catalytic site on the cytosolic surface.