Phospho-R-Smad1/5/8 forms a complex with Co-Smad (R-HSA-201422) [Homo sapiens]


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).

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Literature References
pubMedId Title Journal Year
8893010 Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways Nature 1996
11779505 Structural basis of Smad1 activation by receptor kinase phosphorylation Mol Cell 2001
Inferred Entries
Orthologous events