TGF-β/BMP Pathway |
The TGF-β superfamily regulates a variety of cellular processes including proliferation, differentiation, and apoptosis. Additionally, members of the TGF-β family are also key regulators of embryonic development and tissue differentiation.
TGF-β, bone morphogenic proteins (BMPs), and activins function by activation of a transmembrane serine-threonine kinase receptor composed of type I and type II subunits. In response to ligand binding, the type II subunit phosphorylates and functionally activates the type I subunit. The activated type I subunit subsequently phosphorylates receptor-regulated Smad proteins (R-Smad: Smad1, Smad2, Smad 3, Smad5, and Smad8) on C-terminal serine residues. These activated R-Smad proteins form a heterodimer with Smad4, translocate to the nucleus, and regulate gene expression. I-Smad proteins (Smad6 and Smad7) negatively regulate TGF-β signaling by competing with R-Smads for type I receptor binding sites and recruitment of E3-ubiquitin ligases (Smurf 1 and Smurf 2).
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References |
| 1. |
Attisano, L & Wrana, J.L. Signal transduction by the TGF-b superfamily. Science 296, 1646-1647 (2002). |
| 2. |
Derynck, R. & Zhang, Y.E. Smad-dependent and Smad-independent pathways in TGF-b family signaling. Nature 425, 577-584 (2003). |
| 3. |
Dijke, P. & Hill. C.S. New insights into TGF-b-Smad signaling. Trends Biochem. Sci. 29, 265-273 (2004). |
| 4. |
Shi, Y. & Massague, J. Mechanisms of TGF-b?signaling from cell membrane to the nucleus. Cell 113, 685-700 (2003). |
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