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XB-ART-15368
Genes Dev January 15, 1998; 12 (2): 186-97.

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



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.

PubMed ID: 9436979
PMC ID: PMC316444
Article link: Genes Dev
Grant support: [+]
Genes referenced: acta4 actc1 actl6a ag1 bmp2 bmpr2 cat.2 gad1.2 gsc lgals4.2 ncoa3 nrp1 rpl17 smad1 smad2 smad4.1 smad4.2 smad6 smad6.2 smad7 tbx2 tbxt ventx1.2


Article Images: [+] show captions
References:
Attisano, 1996, Pubmed [+]


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