The phosphorylated C-terminal tail of R-SMAD induces a conformational change in the MH2 domain (Qin et al. 2001, Chacko et al. 2004), which now acquires high affinity towards Co-SMAD i.e. SMAD4 (common mediator of signal transduction in TGF-beta/BMP signaling). The R-SMAD:Co-SMAD complex (Nakao et al. 1997) most likely is a trimer of two R-SMADs with one Co-SMAD (Kawabata et al. 1998). It is important to note that the Co-SMAD itself cannot be phosphorylated as it lacks the C-terminal serine motif.
ZFYVE16 (endofin) promotes SMAD heterotrimer formation. ZFYVE16 can bind TGFBR1 and facilitate SMAD2 phosphorylation, and it can also bind SMAD4, but the exact mechanism of ZFYVE16 (endofin) action in the context of TGF-beta receptor signaling is not known (Chen et al. 2007).
|IntAct||IM-20987-11, IM-20987-9, IM-20987-4, MINT-8308457, MINT-8308499, IM-16611-5, MINT-8200333, IM-16608-3, IM-15364-2384, IM-15364-576, IM-19222-10, IM-19222-6, IM-19222-2, IM-12159-17, EBI-1040178|rcsb, pdb:1U7F, MINT-61949, MINT-61708, IM-23305-6, IM-20987-12, IM-20987-10, IM-20987-8, IM-20987-5, IM-16608-1, IM-16608-2, IM-15364-2382, IM-19222-9, IM-19222-5, IM-19222-1, IM-12159-6, IM-12159-5, IM-12159-18, IM-12159-9, MINT-6799119, EBI-1040189|rcsb, pdb:1U7V, MINT-61945, MINT-15900|
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|11779505||Structural basis of Smad1 activation by receptor kinase phosphorylation||Mol Cell||2001|
|15350224||Structural basis of heteromeric smad protein assembly in TGF-beta signaling||Mol Cell||2004|
|11779503||Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.||Mol Cell||2001|
|17272273||Endofin, a FYVE domain protein, interacts with Smad4 and facilitates transforming growth factor-beta signaling||J. Biol. Chem.||2007|