Transforming growth factor β (TGF-β) superfamily signaling transduction are ubiquitous and essential regulators of cellular processes including proliferation, differentiation, migration, as well as physiological processes, including embryonic development, angiogenesis, and wound healing. Alterations in the expression of members of these signaling transduction often result in human disease.
TGF-beta superfamily is comprised of a large group of proteins, including the activin/inhibin family, bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs), the TGF-beta subfamily (TGF-β), and glial cell line-derived neurotrophic factor (GDNF) family.
As the two major branches TGF-βs (or TGF-β proteins) and bone morphogenetic proteins (BMPs) and that these ligands elicit a huge variety signaling transduction in a variety of organisms. Members of the TGF-β family can stimulate proliferation of some cells in culture but more often exert an inhibitory role that can prevent growth, even of some tumor-derived cells.
The BMP subfamily has many roles in vertebrate and invertebrate development that have a number of interesting characteristics, including dose-dependent responses, which allow them to act as morphogens, instructing cell fate according to spatial concentration gradients.
TGF-beta superfamily of cytokines bind to receptors at the cell surface, and recruit two type I receptors and two type II receptors forming a tetrameric complex. Activated TGF-beta superfamily receptors induce a series of phosphorylation cascade, from receptor phosphorylation to subsequent phosphorylation and activation of downstream signal transducer R-Smads (receptor-activated Smads).
Phosphorylated R-Smads form a heteroligomeric (often trimeric) complex with Smad4 (Co-Smad). The Smad complex is imported into the nucleus and regulates the expression of target genes by direct binding to the target gene promoter and/or through the interaction with transcriptional cofactors in a cell-type-specific manner (Figure 1).
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