TGF-beta Superfamily

The Transforming Growth Factor Beta (TGF-beta) superfamily consists of the TGF-beta proteins, Bone Morphogenetic Proteins (BMPs), Growth Differentiation Factors (GDFs), Glial-derived Neurotrophic Factors (GDNFs), Activins, Inhibins, Nodal, Lefty, and Mülllerian Inhibiting Substance (MIS). Ligands of the TGF-beta superfamily form dimers that bind to heterodimeric receptor complexes consisting of type I and type II receptor subunits with serine/threonine kinase domains. Following ligand binding, the type II receptor phosphorylates and activates the type I receptor, initiating a Smad-dependent signaling cascade that induces or represses transcriptional activity. During development, members of the TGF-beta family are required for dorso-ventral patterning, mesoderm induction and patterning, limb bud formation, bone and cartilage formation, neuron differentiation, and the development of a variety of different tissues and organs.