Bone morphogenetic protein (BMP) induces ectopic bone formation, and plays an important role in the development of the viscera. Ligand binding to its receptor induces the formation of a complex in which the Type II BMP receptor phosphorylates and activates the Type I BMP receptor. The Type I BMP receptor then propagates the signal by phosphorylating a family of signal transducers, the Smad proteins. Currently, eight Smad proteins have been cloned (Smad 1-7 and Smad 9). Upon phosphorylation by the BMP Type I receptor, Smad1 can interact with either Smad4 or Smad6. The Smad1-Smad6 complex is inactive; however, the Smad1-Smad4 complex triggers the expression of BMP responsive genes. The ratio between Smad4 and Smad6 in the cell can modulate the strength of the signal transduced by BMP.
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