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The N domain of Smad7 is essential for specific inhibition of transforming growth factor-beta signaling.
J Cell Biol. 2001 Dec 10; 155(6):1017-27.JC

Abstract

Inhibitory Smads (I-Smads) repress signaling by cytokines of the transforming growth factor-beta (TGF-beta) superfamily. I-Smads have conserved carboxy-terminal Mad homology 2 (MH2) domains, whereas the amino acid sequences of their amino-terminal regions (N domains) are highly divergent from those of other Smads. Of the two different I-Smads in mammals, Smad7 inhibited signaling by both TGF-beta and bone morphogenetic proteins (BMPs), whereas Smad6 was less effective in inhibiting TGF-beta signaling. Analyses using deletion mutants and chimeras of Smad6 and Smad7 revealed that the MH2 domains were responsible for the inhibition of both TGF-beta and BMP signaling by I-Smads, but the isolated MH2 domains of Smad6 and Smad7 were less potent than the full-length Smad7 in inhibiting TGF-beta signaling. The N domains of I-Smads determined the subcellular localization of these molecules. Chimeras containing the N domain of Smad7 interacted with the TGF-beta type I receptor (TbetaR-I) more efficiently, and were more potent in repressing TGF-beta signaling, than those containing the N domain of Smad6. The isolated N domain of Smad7 physically interacted with the MH2 domain of Smad7, and enhanced the inhibitory activity of the latter through facilitating interaction with TGF-beta receptors. The N domain of Smad7 thus plays an important role in the specific inhibition of TGF-beta signaling.

Authors+Show Affiliations

Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo 170-8455, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11739411

Citation

Hanyu, A, et al. "The N Domain of Smad7 Is Essential for Specific Inhibition of Transforming Growth Factor-beta Signaling." The Journal of Cell Biology, vol. 155, no. 6, 2001, pp. 1017-27.
Hanyu A, Ishidou Y, Ebisawa T, et al. The N domain of Smad7 is essential for specific inhibition of transforming growth factor-beta signaling. J Cell Biol. 2001;155(6):1017-27.
Hanyu, A., Ishidou, Y., Ebisawa, T., Shimanuki, T., Imamura, T., & Miyazono, K. (2001). The N domain of Smad7 is essential for specific inhibition of transforming growth factor-beta signaling. The Journal of Cell Biology, 155(6), 1017-27.
Hanyu A, et al. The N Domain of Smad7 Is Essential for Specific Inhibition of Transforming Growth Factor-beta Signaling. J Cell Biol. 2001 Dec 10;155(6):1017-27. PubMed PMID: 11739411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The N domain of Smad7 is essential for specific inhibition of transforming growth factor-beta signaling. AU - Hanyu,A, AU - Ishidou,Y, AU - Ebisawa,T, AU - Shimanuki,T, AU - Imamura,T, AU - Miyazono,K, Y1 - 2001/12/10/ PY - 2001/12/12/pubmed PY - 2002/1/16/medline PY - 2001/12/12/entrez SP - 1017 EP - 27 JF - The Journal of cell biology JO - J Cell Biol VL - 155 IS - 6 N2 - Inhibitory Smads (I-Smads) repress signaling by cytokines of the transforming growth factor-beta (TGF-beta) superfamily. I-Smads have conserved carboxy-terminal Mad homology 2 (MH2) domains, whereas the amino acid sequences of their amino-terminal regions (N domains) are highly divergent from those of other Smads. Of the two different I-Smads in mammals, Smad7 inhibited signaling by both TGF-beta and bone morphogenetic proteins (BMPs), whereas Smad6 was less effective in inhibiting TGF-beta signaling. Analyses using deletion mutants and chimeras of Smad6 and Smad7 revealed that the MH2 domains were responsible for the inhibition of both TGF-beta and BMP signaling by I-Smads, but the isolated MH2 domains of Smad6 and Smad7 were less potent than the full-length Smad7 in inhibiting TGF-beta signaling. The N domains of I-Smads determined the subcellular localization of these molecules. Chimeras containing the N domain of Smad7 interacted with the TGF-beta type I receptor (TbetaR-I) more efficiently, and were more potent in repressing TGF-beta signaling, than those containing the N domain of Smad6. The isolated N domain of Smad7 physically interacted with the MH2 domain of Smad7, and enhanced the inhibitory activity of the latter through facilitating interaction with TGF-beta receptors. The N domain of Smad7 thus plays an important role in the specific inhibition of TGF-beta signaling. SN - 0021-9525 UR - https://www.unboundmedicine.com/medline/citation/11739411/The_N_domain_of_Smad7_is_essential_for_specific_inhibition_of_transforming_growth_factor_beta_signaling_ L2 - https://rupress.org/jcb/article-lookup/doi/10.1083/jcb.200106023 DB - PRIME DP - Unbound Medicine ER -