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.
Nakao, A, Afrakhte, M, Moren, A, Nakayama, T, Christian, JL, Heuchel, R, Itoh, S, Kawabata, M, Heldin, NE, Heldin, CH, ten Dijke, P
Hayashi, H, Abdollah, S, Qiu, Y, Cai, J, Xu, YY, Grinnell, BW, Richardson, MA, Topper, JN, Gimbrone MA, Jr, Wrana, JL, Falb, D
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