骨研究ジャーナル
オープンアクセス

概要

Bone Morphogenetic Protein Receptors: Structure, Function, and Targeting

Joseph Walker

BMPs (Bone Morphogenetic Proteins) are released cytokines that regulate cell destiny and function in a variety of cell types. They activate specific BMP type I and type II serine/threonine kinase receptors, such as BMPRIA and BMPRII, to cause cellular responses. Three type II and four type I receptors have been identified as Activin Receptor-Like Kinases (ALKs). The type II kinase, which is constitutively active, phosphorylates the type I receptor, which activates intracellular signalling by phosphorylating SMAD effectors. Auxiliary cell surface receptors such as Endoglin and Repulsive Guidance Molecules (RGM), which lack inherent enzymatic motifs, can fine-tune signalling by controlling the interaction of BMP ligands with BMPRs. The functional annotation of the BMPR producing genes has aided in the understanding of the underlying mechanisms of disorders caused by mutations in these genes. BMPRII, Endoglin, and RGMc loss of function mutations have been related to pulmonary arterial hypertension, hereditary hemorrhagic telangiectasia, and juvenile hemochromatosis, respectively.