Zeitschrift für Knochenforschung
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Abstrakt

Structure, Function, and Targeting of Bone Morphogenetic Protein Receptors

Joseph Walker

BMPs(BoneMorphogenetic Proteins) are released cytokinesthatregulate cell destiny and functionina variety ofcelltypes. 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 isconstitutively 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 disorderscaused by mutations in these genes. BMPRII, Endoglin, and RGMcloss of function mutations have been related to pulmonary arterial hypertension, hereditary hemorrhagic telangiectasia, and juvenile hemochromatosis,respectively.