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Genes Dev. 1998 Jan 15;12(2):186-97.

Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor.

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  • 1Cell Biology Program, Howard Hughes Medical Institute and The Sloan-Kettering Division of the Cornell University Graduate School of Medical Sciences, Memorial Sloan-Kettering Cancer Center, The Rockefeller University, New York, NY 10021, USA.

Abstract

Bone morphogenetic protein (BMP) receptors signal by phosphorylating Smad1, which then associates with Smad4; this complex moves into the nucleus and activates transcription. Here we report the existence of a natural inhibitor of this process, Smad6, a longer version of the previously reported JV15-1. In Xenopus embryos and in mammalian cells, Smad6 specifically blocks signaling by the BMP/Smad1 pathway. Smad6 inhibits BMP/Smad1 signaling without interfering with receptor-mediated phosphorylation of Smad1. Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy.

PMID:
9436979
PMCID:
PMC316444
[PubMed - indexed for MEDLINE]
Free PMC Article
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