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Updated: Mar 10, 2026

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Published on: October 27, 2020
Regulation of TGF-β Family Signaling by Inhibitory Smads
Keiji Miyazawa1, Kohei Miyazono2
1Department of Biochemistry, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
Abstract:
Inhibitory Smads (I-Smads) have conserved carboxy-terminal MH2 domains but highly divergent amino-terminal regions when compared with receptor-regulated Smads (R-Smads) and common-partner Smads (co-Smads). Smad6 preferentially inhibits Smad signaling initiated by the bone morphogenetic protein (BMP) type I receptors ALK-3 and ALK-6, whereas Smad7 inhibits both transforming growth factor β (TGF-β)- and BMP-induced Smad signaling. I-Smads also regulate some non-Smad signaling pathways. Here, we discuss the vertebrate I-Smads, their roles as inhibitors of Smad activation and regulators of receptor stability, as scaffolds for non-Smad signaling, and their possible roles in the nucleus. We also discuss the posttranslational modification of I-Smads, including phosphorylation, ubiquitylation, acetylation, and methylation.
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