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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Bone Morphogenetic Protein Receptors
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Bone Morphogenetic Proteins / antagonists & inhibitors
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COS Cells
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Cells, Cultured
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DNA-Binding Proteins / antagonists & inhibitors*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Ectoderm / physiology
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Genes, Tumor Suppressor / physiology
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Humans
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Immunoblotting
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Molecular Sequence Data
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Nerve Growth Factors
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Receptors, Cell Surface / physiology
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Receptors, Growth Factor*
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Signal Transduction / genetics
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Smad Proteins
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Smad1 Protein
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Smad4 Protein
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Smad6 Protein
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Trans-Activators / physiology
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Transfection
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Xenopus
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Xenopus Proteins*
Substances
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Bone Morphogenetic Proteins
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DNA-Binding Proteins
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MXD1 protein, Xenopus
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Nerve Growth Factors
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Receptors, Cell Surface
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Receptors, Growth Factor
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SMAD1 protein, human
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SMAD4 protein, human
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SMAD6 protein, human
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Smad Proteins
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Smad1 Protein
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Smad4 Protein
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Smad6 Protein
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Smad6 protein, Xenopus
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Trans-Activators
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Xenopus Proteins
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smad4.1 protein, Xenopus
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smad4.2 protein, Xenopus
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Bone Morphogenetic Protein Receptors