Bone Morphogenetic Protein-3 Family Members and their Biological Functions

Bone morphogenetic protein-3 and 3b (BMP-3 and BMP-3b) together represent a unique subgroup of the BMP family. BMP-3b shares 82% amino acid identity with BMP-3 in the mature region (ligand domain), but only 37% in the pro-region (pro-domain). In osteoblasts, BMP-3 and 3b have similar antagonistic activity against BMP-2, but they are differentially regulated. In developing embryos, BMP-3 and 3b have different dorsalizing activities. BMP-3b triggers secondary head formation in an autonomous manner, whereas BMP-3 induces aberrant tail formation. Loss-of-function analysis demonstrates that coordinated activity of xBMP-3b and cerberus, a head inducer, are required for head formation in Xenopus embryos. At the molecular level, BMP-3b antagonizes both nodal-like proteins (Xnr1 and derriere) and ventralizing BMPs (BMP-2 and ADMP), whereas BMP-3 only antagonizes ventralizing BMPs. Moreover, BMP-3b, but not BMP-3, associates with the monomeric form of Xnr1, a nodal-like protein. These molecular features of BMP-3 and 3b are due to their distinct pro-regions. These findings suggest that the processing of precursor regions and assembly of BMP-3 and 3b are important in various developmental processes and organogenesis.