Clinical significance linked to functional defects in bone morphogenetic protein type 2 receptor, BMPR2

Abstract

Bone morphogenetic protein type 2 receptor (BMPR2) is oneof the transforming growth factor-β (TGF-β) superfamilyreceptors, performing diverse roles during embryonic development, vasculogenesis, and osteogenesis. Human BMPR2consists of 1,038 amino acids, and contains functionallyconserved extracellular, transmembrane, kinase, and C-terminalcytoplasmic domains. Bone morphogenetic proteins (BMPs)engage the tetrameric complex, composed of BMPR2 and itscorresponding type 1 receptors, which initiates SMADproteins-mediated signal transduction leading to the expressionof target genes implicated in the development ordifferentiation of the embryo, organs and bones. In particular, genetic alterations of BMPR2 gene are associated with severalclinical disorders, including representative pulmonary arterialhypertension, cancers, and metabolic diseases, thus demonstratingthe physiological importance of BMPR2. In this minireview, we summarize recent findings regarding the molecularbasis of BMPR2 functions in BMP signaling, and the versatileroles of BMPR2. In addition, various aspects of experimentallyvalidated pathogenic mutations of BMPR2 and the linkedhuman diseases will also be discussed, which are important inclinical settings for diagnostics and treatment.