Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor.
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.
Mesh Terms:
Amino Acid Sequence, Animals, Bone Morphogenetic Protein Receptors, Bone Morphogenetic Proteins, COS Cells, Cells, Cultured, DNA-Binding Proteins, Ectoderm, Genes, Tumor Suppressor, Humans, Immunoblotting, Molecular Sequence Data, Receptors, Cell Surface, Receptors, Growth Factor, Signal Transduction, Smad Proteins, Smad1 Protein, Smad4 Protein, Smad6 Protein, Trans-Activators, Transfection, Xenopus, Xenopus Proteins
Amino Acid Sequence, Animals, Bone Morphogenetic Protein Receptors, Bone Morphogenetic Proteins, COS Cells, Cells, Cultured, DNA-Binding Proteins, Ectoderm, Genes, Tumor Suppressor, Humans, Immunoblotting, Molecular Sequence Data, Receptors, Cell Surface, Receptors, Growth Factor, Signal Transduction, Smad Proteins, Smad1 Protein, Smad4 Protein, Smad6 Protein, Trans-Activators, Transfection, Xenopus, Xenopus Proteins
Genes Dev.
Date: Jan. 15, 1998
PubMed ID: 9436979
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