Phospho-R-Smad1/5/8 forms a complex with Co-Smad

Stable Identifier
Homo sapiens
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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).

SARS-CoV-1 nucleocapsid protein (N) associates with SMAD3 and this binding interferes with the complex formation between SMAD3 and SMAD4. By this mechanism N modulates TGF-beta signaling to block apoptosis of SARS-CoV-infected host cells (Zhao et al. 2008).

Literature References
PubMed ID Title Journal Year
11779505 Structural basis of Smad1 activation by receptor kinase phosphorylation

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

Mol Cell 2001
8893010 Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways

Massague, J, Lagna, G, Hemmati-Brivanlou, A, Hata, A

Nature 1996
Orthologous Events
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