title: EGF-CFC proteins are essential coreceptors for the TGF-beta signals Vg1 and GDF1.
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.
authors.affiliation: Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Simon K
authors.initials: SK
authors.lastname: Cheng
authors.forename: Felix
authors.initials: F
authors.lastname: Olale
authors.forename: James T
authors.initials: JT
authors.lastname: Bennett
authors.forename: Ali H
authors.initials: AH
authors.lastname: Brivanlou
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000502:physiology; D030301:Activin Receptors, Type II / Q000502:physiology*; D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D004815:Epidermal Growth Factor; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000502:physiology*; D055412:Growth Differentiation Factors; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology; D055457:Nodal Protein; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013045:Species Specificity; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D019485:Bone Morphogenetic Proteins; C513103:GDF1 protein, Xenopus; C492266:GDF11 protein, human; D058851:GPI-Linked Proteins; C119153:Gdf11 protein, mouse; C079678:Gdf3 protein, zebrafish; D006023:Glycoproteins; D055412:Growth Differentiation Factors; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; D011506:Proteins; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; C489450:Tdgf1 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C110484:tdgf1 protein, zebrafish; C096788:tdgf1.3 protein, Xenopus; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; D052005:Bone Morphogenetic Protein Receptors, Type I; C425584:activin receptor type II-B