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

First Author  Cheng SK Year  2004
Journal  PLoS Biol Volume  2
Issue  2 Pages  E30
PubMed ID  14966532 Mgi Jnum  J:245350
Mgi Id  MGI:5918418 Doi  10.1371/journal.pbio.0020030
Citation  Cheng SK, et al. (2004) Lefty blocks a subset of TGFbeta signals by antagonizing EGF-CFC coreceptors. PLoS Biol 2(2):E30
abstractText  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.
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