FIGURE 1.

Diagram represents the ligand specificity and physiological function(s) of GC-A/NPRA. The ligand-binding to NPRA generates second messenger cGMP from the hydrolysis of GTP. An increased level of intracellular cGMP is produced, which activates three known cGMP effecter molecules namely; cGMP-dependent protein kinases (PKGs), cGMP-dependent phosphodiesterases (PDEs), and cGMP-dependent ion-gated channels (CNGs). The ANP/NPRA/cGMP signaling may antagonize a number of pathways including; intracellular formation of cAMP, Ca²⁺, IP_3; cytokine expression; and the activation of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs). The resulting signaling cascade can mimic the physiological responses of ANP/NPRA. LBD, ligand binding domain; TM transmembrane region; protein-KHD, protein kinase-like homology domain; and GCD, guanylyl cyclase catalytic domain; DD, dimerization domain of NPRA and NPRB. The ligand binding region, transmembrane domain, and small intracellular tail region of NPRC are indicated.