Structure, regulation and functions of particulate guanylyl cyclase type A

Abstract

Guanylyl cyclase type A (GC-A) belongs to the particulate guanylyl cyclases (pGC), which, like the soluble guanylyl cyclases (sGC), catalyze the synthesis of a common secondary messenger, namely cyclic GMP (cGMP), involved in many cellular processes. Although both forms of guanylyl cyclases produce the same secondary messenger, activation of each of them triggers different signaling pathways leading to different cellular effects. This indicates that the final effect of cGMP depends on the site of its synthesis in the cell (cytosol or cell membrane). Particulate guanylyl cyclase type A is a homodimeric protein activated by natriuretic peptides (ANP - atrial natriuretic peptide and BNP - brain natriuretic peptide) binding in the extracellular domain of the enzyme. The widespread expression of GC-A in different cell types and tissues suggests that this protein may regulate many cellular processes. Besides the role of GC-A in the cardiovascular system, which is the most thoroughly documented in the literature, it was observed that this protein is also involved in carcinogenesis and regulation of inflammatory reactions. This review describes important information about the structure, functions and regulation of GC-A catalytic activity, and the regulation of GC-A gene expression.