Рецепторные гуанилатциклазы

Representation of hormone specificity and physiological and pathophysiological function(s) of GC-A/NPRA

After ligand-binding, GC-A/NPRA is shown to generate second messenger cGMP from the hydrolysis of GTP. An increased level of i-cGMP stimulates and activates cGMP-dependent protein kinases (PKGs), cGMP-dependent phosphodiesterases (PDEs), and cGMP-dependent ion-gated channels (CNGs). The cGMP-dependent signaling may antagonize a number of pathways including; intracellular Ca²⁺ release, IP₃ formation, activation of PKC and MAPKs, and production of TNF-α and interleukin-6. The resulting cascade can mimic ANP/NPRA/cGMP-dependent responses in both physiological and pathophysiological environments. The activation of NPRC may lead to a decrease in cAMP levels and an increase in IP₃ production. The ligand binding domain (LBD), TM, and intracellular protein kinase-like homology domain (KHD) and guanylyl cyclase catalytic domain (GCD) of GC-A/NPRA are shown. DD - the dimerization domain of NPRA.

Comparison of amino-acid sequence of human ANP, BNP, and CNP with conserved amino acid residues, which are represented by shaded boxes. The lines between two cysteine residues in ANP, BNP, and CNP indicate a 17-amino acid disulfide bridge, which is essential for the biological activity of three natriuretic peptide hormones. ANF, atrial natriuretic peptide; BNP, brain natriuretic peptide; and CNP, C-type natriuretic peptide.

Дата добавления: 2014-01-14