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Smad7 inhibits transforming growth factor-beta family type i receptors through two distinct modes of interaction.


ABSTRACT: The inhibitory Smads (I-Smads), i.e. Smad6 and Smad7, are negative regulators of transforming growth factor-? (TGF-?) family signaling. I-Smads inhibit TGF-? family signaling principally through physical interaction with type I receptors (activin receptor-like kinases), so as to compete with receptor-regulated Smads (R-Smads) for activation. However, how I-Smads interact with type I receptors is not well understood. In the present study, we found that Smad7 has two modes of interaction with type I receptors. One is through a three-finger-like structure in the MH2 domain, consisting of residues 331-361, 379-387, and the L3 loop. The other is through a basic groove in the MH2 domain (Mochizuki, T., Miyazaki, H., Hara, T., Furuya, T., Imamura, T., Watabe, T., and Miyazono, K. (2004) J. Biol. Chem. 279, 31568-31574). We also found that Smad6 principally utilizes a basic groove in the MH2 domain for interaction with type I receptors. Smad7 thus has an additional mode of interaction with TGF-? family type I receptors not possessed by Smad6, which may play roles in mediating the inhibitory effects unique to Smad7.

SUBMITTER: Kamiya Y 

PROVIDER: S-EPMC2945574 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Smad7 inhibits transforming growth factor-beta family type i receptors through two distinct modes of interaction.

Kamiya Yuto Y   Miyazono Kohei K   Miyazawa Keiji K  

The Journal of biological chemistry 20100727 40


The inhibitory Smads (I-Smads), i.e. Smad6 and Smad7, are negative regulators of transforming growth factor-β (TGF-β) family signaling. I-Smads inhibit TGF-β family signaling principally through physical interaction with type I receptors (activin receptor-like kinases), so as to compete with receptor-regulated Smads (R-Smads) for activation. However, how I-Smads interact with type I receptors is not well understood. In the present study, we found that Smad7 has two modes of interaction with type  ...[more]

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