BMP-4

BMP4 is a TGFβ superfamily ligand that is widely expressed from early embryogenesis through adulthood. It plays an important role in mesenchyme formation, epidermal determination, suppression of neural induction, the development of multiple organs, and tissue repair. The human BMP4 precursor contains a 273 amino acid (aa) propeptide and a 116 aa mature protein. Processing of the propeptide by furin or proprotein convertase 6 enables the formation of the mature disulfidelinked homodimeric BMP4 and facilitates its secretion. Similar intracellular processes may lead to the formation and recreation of BMP4/BMP7 disulfidelinked heterodimer. Mature human and mouse BMP4 share 98% aa sequence identity. Human BMP4 shares 85% aa sequence identity with human BMP2 and less than 50% with other human BMPs. Compared to BMP4 homodimers, BMP4/ BMP7 heterodimers exhibit a greater potency in inducing osteogenic differentiation. In Xenopus, the heterodimers can also induce the formation of mesoderm, whereas BMP4 homodimers only provide ventralizing signals for existing mesoderm. BMP4 signals through tetrameric complexes composed of type I (primarily Activin RIA or BMPRIA) and type II (primarily Activin RIIA or BMPRII) receptors. The bioavailability of BMP4 is regulated by its interaction with multiple proteins and glycosaminoglyca) .