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

PLoS Biol. 2004 Feb;2(2):E30. doi: 10.1371/journal.pbio.0020030. Epub 2004 Feb 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Embryo, Nonmammalian / physiology
  • Gene Expression Regulation, Developmental*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Molecular Sequence Data
  • Receptors, Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / genetics*
  • Xenopus / embryology
  • Xenopus Proteins / genetics


  • CFC1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Xenopus Proteins

Associated data

  • GENBANK/Z22536
  • SWISSPROT/P08476
  • SWISSPROT/P09534
  • SWISSPROT/P20863
  • SWISSPROT/P23359
  • SWISSPROT/P27040
  • SWISSPROT/P38445
  • SWISSPROT/P43021
  • SWISSPROT/P51865
  • SWISSPROT/P53544
  • SWISSPROT/P57785
  • SWISSPROT/P87358
  • SWISSPROT/P97474
  • SWISSPROT/P97766
  • SWISSPROT/P97946
  • SWISSPROT/Q07998
  • SWISSPROT/Q64280
  • SWISSPROT/Q91350