BMP pathway: Smadl, Smad5, Smad8

TGF-p, activin pathways: Smad2, Smad3


TGF-p, activin, BMP pathways: Smad4

Inhibitory Smads |

BMP pathway: Smad6

TGF-[3, activin. BMPpathways: Smad7

Fig.11.2 The Smad family can be divided into three structurally and functionally distinct groups. One group includes receptor regulated Smads (R-Smads). These Smads contain the SSXS motif at the C-tail for phosphorylation by receptors. Smadl, Smad5 and Smad8 are phosphorylated by BMP receptors, whereas Smad2 and Smad3 are phosphorylated by the homologous TGF -(3 and activin receptors, Smad4 is a common Smad (Co-Smad) that participates in TGF-p, activin and BMP signaling by associating with a receptor-phosphorylated Smad. In mammalian cells, Smad4 is the only Co-Smad. The third group includes those inhibitory Smads (I-Smads) that antagonize TGF-P family signaling. Smad6 specifically inhibits BMP signaling. Smad7 inhibits TGF-P, activin and BMP signaling. The N-terminal and C-terminal domains are also termed as MHl (Mad Homology 1) and MH2 (Mad Homology 2) domains, respectively. The MHl and MH2 domains are conserved among R-Smads and Smad4. The MH2 domain is also similar in Smad6 and Smad7. The MHl domains of Smad6 and Smad7 are not conserved with those of the R-Smads and Smad4.

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