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PLoS Biol February 1, 2004; 2 (2): E30.

Lefty blocks a subset of TGFbeta signals by antagonizing EGF-CFC coreceptors.

Cheng SK , Olale F , Brivanlou AH , Schier AF .

Members of the EGF-CFC family play essential roles in embryonic development and have been implicated in tumorigenesis. The TGFbeta signals Nodal and Vg1/GDF1, but not Activin, require EGF-CFC coreceptors to activate Activin receptors. We report that the TGFbeta signaling antagonist Lefty also acts through an EGF-CFC-dependent mechanism. Lefty inhibits Nodal and Vg1 signaling, but not Activin signaling. Lefty genetically interacts with EGF-CFC proteins and competes with Nodal for binding to these coreceptors. Chimeras between Activin and Nodal or Vg1 identify a 14 amino acid region that confers independence from EGF-CFC coreceptors and resistance to Lefty. These results indicate that coreceptors are targets for both TGFbeta agonists and antagonists and suggest that subtle sequence variations in TGFbeta signals result in greater ligand diversity.

PubMed ID: 14966532
PMC ID: PMC340941
Article link: PLoS Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: acvr1b acvr2b ass1 egf fgd1 gdf1 gsc igf2bp3 kcnj2 lefty myc nodal nodal1 ptpn11 smad2 tbx2 tbxt tdgf1.3 tgfb1 tspan31 vegfa vegfd

Article Images: [+] show captions
References [+] :
Adkins, Antibody blockade of the Cripto CFC domain suppresses tumor cell growth in vivo. 2003, Pubmed