Transforming growth factors bone morphogenetic proteins

Transforming growth factor (3 (TGF(3) (that suppresses cell proliferation), the related develop-mentally important activins (involved in mesoderm induction) and bone morphogenetic proteins (involved in bone formation) act via PM-located transmembrane receptors that are Ser/Thr-specific PKs. Thus, TGF(3 binds to the extracellular domain of a specific TGF(3 receptor with the successive consequences of activation of the receptor Ser/Thr-specific PK activity, phosphorylation of a protein Mad to yield P-Mad and downstream consequences resulting in developmentally important specific gene expression. Thus, dorso-ventral differentiation in Xenopus embryos involves Mad-like proteins and a Mad-like gene is a tumour suppressor gene. 

Fig. 6.5 Signalling through SMAD proteins. Receptor complexes, formed with transforming growth factor.p (TGF-p) and related factors, activins, and bone morphogenetic proteins (BMPs), consist of two serine/threonine receptor kinases, the type II and type I receptors. Binding of the ligand results In autophosphorylation of type I receptors. The activated type I receptors in turn phosphoryiate and activate R-SMADs SMADs 1,...

These receptors have a cysteine-rich extraceUular domain and a cytoplasmic serine/threonine kinase activity.Transforming growth factor-P (TGF-P) superfamily induces growth arrest in epithelial cells. In addition to the three TGF-P isoforms, this family comprises activins, bone morphogenetic proteins and other secreted factors. 

Three major families of growth factors, namely, bone morphogenetic proteins (BMPs), members of transforming growth factor P-family, the Wnt family, as well as the fibroblast growth factor family, play an important role in cardiogenesis [101]. 

Harland, R. (1995) The transforming growth factor b family and induction of the vertebrate mesoderm bone morphogenetic proteins are ventral inducers. Proc. Natl Acad. ScL USA 91,10,243-10,246. 

---