Mechanisms of BMP-Receptor Interaction and Activation

Bone morphogenetic proteins (BMPs), together with the eponymous transforming growth factor (TGF) β and the Activins form the TGFβ superfamily of ligands. This protein family comprises more than 30 structurally highly related proteins, which determine formation, maintenance, and regeneration of tissues and organs. Their importance for the development of multicellular organisms is evident from their existence in all vertebrates as well as nonvertebrate animals. From their highly specific functions in vivo either a strict relation between a particular ligand and its cognate cellular receptor and/or a stringent regulation to define a distinct temperospatial expression pattern for the various ligands and receptor is expected. However, only a limited number of receptors are found to serve a large number of ligands thus implicating highly promiscuous ligand-receptor interactions instead. Since in tissues a multitude of ligands are often found, which signal via a highly overlapping set of receptors, this raises the question how such promiscuous interactions between different ligands and their receptors can generate concerted and highly specific cellular signals required during embryonic development and tissue homeostasis.