Evidence map›Paper›PMID 12052855›Full record

ArticleMolecular and cellular biology2002

Dual roles of Cripto as a ligand and coreceptor in the nodal signaling pathway.

Yu-Ting Yan, Jan-Jan Liu, Yi Luo, Chaosu E, Robert S Haltiwanger, Cory Abate-Shen, Michael M Shen

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 208 citations in OpenAlex.

  1. Article
  2. Article
  3. Activin Actions in Adipocytes.The Journal of clinical endocrinology and metabolism · 2025
    Review
  4. ProteinMolecules (Basel, Switzerland) · 2025
    Review
  5. Review
  6. Cripto-1 acts as a molecular bridge linking nodal to ALK4 via distinct structural domains.Protein science : a publication of the Protein Society · 2025
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development.International journal of molecular sciences · 2023
    Article
  15. Article
  16. A novel biallelic loss-of-function variant inCold Spring Harbor molecular case studies · 2022
    Article
  17. Article
  18. Article
  19. Article
  20. Review

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Yu-Ting YanCenter for Advanced Biotechnology and Medicine and Department of Pediatric, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Jan-Jan Liu
Yi Luo
Chaosu E
Robert S Haltiwanger
Cory Abate-Shen
Michael M Shen
State University of New York · USAdvanced Pharma · USJohnson University · US

Funding

O-Glycosylation of Epidermal Growth Factor-like MotifsR01GM061126 · NIGMS · UNIVERSITY OF GEORGIA · PI HALTIWANGER, ROBERT S. · 2001 to 2021
$9.1M
Roles for MSX1 in vertebrate embryogenesisR01HD029446 · NICHD · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ABATE-SHEN, CORY · 1992 to 2007
$2.2M
EGF CFC GENES IN MAMMALIAN LEFT RIGHT AXIS DETERMINATIONR01HD038766 · NICHD · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI SHEN, MICHAEL M. · 2000 to 2004
$1.6M
CRIPTO FUNCTION IN MURINE CARDIAC DEVELOPMENT.R01HL060212 · NHLBI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI SHEN, MICHAEL M. · 1998 to 2001
$606k
NHLBI NIH HHS HL60212NICHD NIH HHS HD29446NICHD NIH HHS HD38766NICHD NIH HHS R01 HD029446NICHD NIH HHS R01 HD038766NIGMS NIH HHS GM61126NIGMS NIH HHS R01 GM061126
6 · The paper itself

Abstract

The EGF-CFC gene Cripto encodes an extracellular protein that has been implicated in the signaling pathway for the transforming growth factor beta (TGF beta) ligand Nodal. Although recent findings in frog and fish embryos have suggested that EGF-CFC proteins function as coreceptors for Nodal, studies in cell culture have implicated Cripto as a growth factor-like signaling molecule. Here we reconcile these apparently disparate models of Cripto function by using a mammalian cell culture assay to investigate the signaling activities of Nodal and EGF-CFC proteins. Using a luciferase reporter assay, we found that Cripto has activities consistent with its being a coreceptor for Nodal. However, Cripto can also function as a secreted signaling factor in cell coculture assays, suggesting that it may also act as a coligand for Nodal. Furthermore, we found that the ability of Cripto to bind to Nodal and mediate Nodal signaling requires the addition of an O-linked fucose monosaccharide to a conserved site within EGF-CFC proteins. We propose a model in which Cripto has dual roles as a coreceptor as well as a coligand for Nodal and that this signaling interaction with Nodal is regulated by an unusual form of glycosylation. Our findings highlight the significance of extracellular modulation of ligand activity as an important means of regulating TGF beta signaling pathways during vertebrate development.

Indexed as

Epidermal Growth FactorMembrane GlycoproteinsProteinsActivin Receptors, Type IAmino Acid MotifsCells, CulturedCross-Linking ReagentsGlycosylationGPI-Linked ProteinsHumansIntercellular Signaling Peptides and ProteinsLuciferasesMutationNeoplasm ProteinsNodal ProteinRecombinant ProteinsActivin Receptors, Type IACVR1 protein, humanCross-Linking ReagentsEpidermal Growth FactorGPI-Linked ProteinsIntercellular Signaling Peptides and ProteinsLuciferasesMembrane GlycoproteinsNeoplasm ProteinsNodal ProteinNODAL protein, humanProteinsRecombinant ProteinsTDGF1 protein, humanTransforming Growth Factor beta

Identifiers

PMID12052855
PMCPMC133918
OpenAlexW2104633606

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.