Natriuretic peptide receptor B (NPR-B) (NPR-B)

Natriuretic peptide receptor B (NPR-B), also known as Guanylate cyclase B (GC-B), is a transmembrane protein that functions as both a receptor and an enzyme (UniProt P20648). It is primarily expressed in the growth plate of bones and is the principal receptor for C-type natriuretic peptide (CNP) (NCBI Gene 4882). Upon binding of CNP, the intracellular guanylate cyclase domain of NPR-B catalyzes the production of cyclic GMP (cGMP) from GTP. This increase in cGMP levels acts as a second messenger that inhibits the mitogen-activated protein kinase (MAPK) pathway, which is a key negative regulator of chondrocyte proliferation and differentiation (PMID: 17030507). Consequently, NPR-B signaling is essential for normal longitudinal bone growth. Mutations in the NPR2 gene, which encodes this receptor, lead to various skeletal disorders; loss-of-function mutations result in acromesomelic dysplasia, while gain-of-function mutations cause overgrowth syndromes (PMID: 25707441). In the context of achondroplasia, NPR-B is a therapeutic target for CNP analogs like vosoritide, which aim to bypass the inhibitory effects of overactive FGFR3 signaling (PMID: 33113308). Beyond bone growth, NPR-B also plays roles in cardiovascular regulation and fluid balance, though its effects are less pronounced than those of NPR-A.

Other names

Guanylate cyclase BNPR2GC-BAtrial natriuretic peptide receptor 2ANPRBGUCY2BAtrial natriuretic peptide receptor type B

Agonist binding to the extracellular domain of the receptor stimulates the intrinsic intracellular guanylate cyclase activity, leading to the conversion of GTP to cGMP. In chondrocytes, increased cGMP levels inhibit the MAPK/ERK signaling pathway, which is overactive in achondroplasia, thereby promoting bone growth (PMID: 33113308).