Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4

Stable Identifier
R-HSA-170847
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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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).

Literature References
PubMed ID Title Journal Year
9670020 Smad proteins exist as monomers in vivo and undergo homo- and hetero-oligomerization upon activation by serine/threonine kinase receptors

Kawabata, M, Inoue, H, Hanyu, A, Imamura, T, Miyazono, K

EMBO J 1998
11779505 Structural basis of Smad1 activation by receptor kinase phosphorylation

Qin, BY, Chacko, BM, Lam, SS, de Caestecker, MP, Correia, JJ, Lin, K

Mol Cell 2001
17272273 Endofin, a FYVE domain protein, interacts with Smad4 and facilitates transforming growth factor-beta signaling

Chen, YG, Wang, Z, Ma, J, Zhang, L, Lu, Z

J. Biol. Chem. 2007
15350224 Structural basis of heteromeric smad protein assembly in TGF-beta signaling

Chacko, BM, Qin, BY, Tiwari, A, Shi, G, Lam, S, Hayward, LJ, De Caestecker, M, Lin, K

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.

Wu, JW, Hu, M, Chai, J, Seoane, J, Huse, M, Li, C, Rigotti, DJ, Kyin, S, Muir, TW, Fairman, R, Massague, J, Shi, Y

Mol Cell 2001
9311995 TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4

Nakao, A, Souchelnytskyi, S, Kawabata, M, Ishisaki, A, Oeda, E, Tamaki, K, Hanai, J, Heldin, CH, Miyazono, K, ten Dijke, P

EMBO J 1997
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