Prostate-derived factor and growth and differentiation factor-8: newly discovered members of the TGF-β superfamily

The transforming growth factor-β (TGF-β) superfamily is a large group of structurally related proteins that play various important roles during embryonic development, as well as in adult life. This superfamily in addition to TGF-βs also contains the inhibins, activins, Mullerian inhibiting substance, and bone morphogenetic proteins (BMPs), as well as the various growth and differentiation factors (GDFs). Members of the TGF-β superfamily are highly conserved, secreted molecules whose biologically active C-terminal domains play a variety of roles in embryonic pattern formation, body plan establishment and organogenesis in numerous species fromDrosophilaand C.elegansthrough humans [1, 2, 3]. Animals and humans lacking or having mutations in various TGF-β family members exhibit a wide variety of phenotypes, ranging from early embryonic death due to lack of mesodermal development to viable, but severely compromised animals with a variety of skeletal defects, to human diseases such as fibrodysplasia ossificans progressiva and dentinogenesis imperfecta. Among the TGF-s family members, the BMPs form a large subgroup of proteins, which were originally named on the basis of their ability as components of demineralized bone matrix to induce ectopic bone formation. Subsequently , classical protein chemistry in conjunction with molecular biology resulted in the cloning and expression of a number of BMPs. Their extensive homology to each other, in addition to highly conserved structural features, places them in the TFG-β superfamily[4].