BIER, E.; SRINIVASAN, S.: Extracellular Modulation of BMP Signaling

A variety of extracellular modulators of BMP signaling act by binding to BMP ligands. Some of these factors reduce the availability of BMPs by sequestering them and preventing them from gaining access to all or specific subsets of BMP-receptors while others may promote the activities of selected BMPs. One example of a BMP modulator is the Drosophila Short Gastrulation (Sog) protein, which exerts several different influences on BMP signaling. The distinct activities of Sog are associated with different forms of Sog that are created by regulated processing of Sog by metalloproteases such as Tolloid (Tld). Processing of Sog to generate different Sog cleavage products by Tld is regulated by another extracellular protein known as Twisted Gastrulation (Tsg). Tsg binds to Sog and alters the site at which Tld can cleave Sog. This network of protein interactions regulating BMP signaling has been highly conserved during vertebrate and invertebrate evolution and underlies the critical process of neural induction in diverse species. The relevance of these results to general regulation of extracellular signals by hormone-binding proteins (HBPs) will be discussed.