Molecular aspects of soluble guanylyl cyclase regulation

Soluble guanylyl cyclase (sGC) is a heterodimeric enzyme (comprised of α and β subunits) that generates the intracellular second messenger cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). cGMP is subsequently important for the regulation of protein kinases, ion channels, and phosphodiesterases. Since recent evidence has demonstrated that heterodimerization of the α/β subunits is essential for basal and stimulated enzymatic activity, the existence of several types of isoforms for each of the two subunits, along with their varying degrees of expression in different tissues, implies that multiple regulatory mechanisms exist for sGC. Yet, progress in studying and clarifying the regulatory processes that can alter sGC expression and activity has only slowly started being elucidated. In the following paper, we elaborate on sGC structure, function, and distribution along with recently described signaling pathways that modulate sGC gene expression.