EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1

Genes Dev. 2003 Jan 1;17(1):31-6. doi: 10.1101/gad.1041203.

Abstract

The TGF-beta signals Nodal, Activin, GDF1, and Vg1 have been implicated in mesoderm induction and left-right patterning. Nodal and Activin both activate Activin receptors, but only Nodal requires EGF-CFC coreceptors for signaling. We report that Vg1 and GDF1 signaling in zebrafish also depends on EGF-CFC proteins, but not on Nodal signals. Correspondingly, we find that in Xenopus Vg1 and GDF1 bind to and signal through Activin receptors only in the presence of EGF-CFC proteins. These results establish that multiple TGF-beta signals converge on Activin receptor/EGF-CFC complexes and suggest a more widespread requirement for coreceptors in TGF-beta signaling than anticipated previously.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors, Type I / genetics
  • Activin Receptors, Type I / physiology
  • Activin Receptors, Type II / physiology*
  • Animals
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Proteins / physiology*
  • Epidermal Growth Factor*
  • GPI-Linked Proteins
  • Glycoproteins / physiology*
  • Growth Differentiation Factors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Intercellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Membrane Glycoproteins*
  • Membrane Proteins
  • Mice
  • Neoplasm Proteins / physiology
  • Nodal Protein
  • Protein-Serine-Threonine Kinases*
  • Proteins*
  • Receptors, Growth Factor*
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / physiology
  • Recombinant Fusion Proteins / physiology
  • Signal Transduction / physiology
  • Species Specificity
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transforming Growth Factor beta / physiology*
  • Xenopus Proteins*
  • Xenopus laevis / embryology
  • Zebrafish
  • Zebrafish Proteins*

Substances

  • Bone Morphogenetic Proteins
  • GDF1 protein, Xenopus
  • GDF11 protein, human
  • GPI-Linked Proteins
  • Gdf11 protein, mouse
  • Gdf3 protein, zebrafish
  • Glycoproteins
  • Growth Differentiation Factors
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Membrane Glycoproteins
  • Membrane Proteins
  • Neoplasm Proteins
  • Nodal Protein
  • Nodal protein, mouse
  • Proteins
  • Receptors, Growth Factor
  • Receptors, Transforming Growth Factor beta
  • Recombinant Fusion Proteins
  • Tdgf1 protein, mouse
  • Transcription Factors
  • Transforming Growth Factor beta
  • Xenopus Proteins
  • Zebrafish Proteins
  • tdgf1 protein, zebrafish
  • tdgf1.3 protein, Xenopus
  • Epidermal Growth Factor
  • Protein-Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Activin Receptors, Type II
  • Bone Morphogenetic Protein Receptors, Type I
  • activin receptor type II-B