Reactome | I-SMAD competes with SMAD2/3 for type I receptor (TGFBR1)

I-SMAD competes with SMAD2/3 for type I receptor (TGFBR1)

Stable Identifier

R-HSA-173512

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytoplasmic side of plasma membrane

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I-SMAD competes with SMAD2/3 for type I receptor (TGFBR1)

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I-SMADs (SMAD6 and SMAD7) reside in the nucleus presumably to be sequestered from the TGF-beta receptor complex and thus avoid inappropriate silencing of the signaling pathway. Upon activation of the signaling pathway, I-SMADs exit the nucleus and are recruited to the signaling TGF-beta receptor complex. I-SMADs directly bind to the so-called L45 loop of the type I receptor, the site of binding of R-SMADs. Thus, I-SMADs competitively inhibit the activation/phosphorylation of R-SMADs.

Literature References

PubMed ID	Title	Journal	Year
9335507	Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling Nakao, A, Afrakhte, M, Moren, A, Nakayama, T, Christian, JL, Heuchel, R, Itoh, S, Kawabata, M, Heldin, NE, Heldin, CH, ten Dijke, P	Nature	1997
9215638	The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling Hayashi, H, Abdollah, S, Qiu, Y, Cai, J, Xu, YY, Grinnell, BW, Richardson, MA, Topper, JN, Gimbrone MA, Jr, Wrana, JL, Falb, D	Cell	1997