Cited by 299Wnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene RegulationHedgehog Signaling Pathway Studies

Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis

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Rothbächer, Ute, Laurent, Micheline N., Deardorff, Matthew A., Klein, Peter S., Cho, Ken W.Y., Fraser, Scott E.·2000·The EMBO Journal

Abstract

Dishevelled (Dsh) induces a secondary axis and can translocate to the membrane when activated by Frizzleds; however, dominant-negative approaches have not supported a role for Dsh in primary axis formation. We demonstrate that the Dsh protein is post-translationally modified at the dorsal side of the embryo: timing and position of this regulation suggests a role of Dsh in dorsal-ventral patterning in Xenopus. To create functional links between these properties of Dsh we analyzed the influence of endogenous Frizzleds and the Dsh domain dependency for these characteristics. Xenopus Frizzleds phosphorylate and translocate Xdsh to the membrane irrespective of their differential ectopic axes inducing abilities, showing that translocation is insufficient for axis induction. Dsh deletion analysis revealed that axis inducing abilities did not segregate with Xdsh membrane association. The DIX region and a short stretch at the N-terminus of the DEP domain are necessary for axis induction while the DEP region is required for Dsh membrane association and its phosphorylation. In addition, Dsh forms homomeric complexes in embryos suggesting that multimerization is important for its proper function.

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  • The DEP domain is required for membrane translocation of Dsh.

    “The DEP domain is also required for membrane translocation of Dsh.117”

    From Wnt signal transduction pathways (2008) · cites this paper as [117]

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  1. Tsang M., Lijam, N., Yang, Y., Beier, D.R., Wynshaw-Boris, A. and Sussman, D.J. (1996) Isolation and characterization of mouse dishevelled-3. Dev. Dynam., 207, 253–262. [DOI] [PubMed] [Google Scholar]

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Authors
Rothbächer, U., Laurent, M. N., Deardorff, M. A., Klein, P. S., Cho, K. W. Y., & Fraser, S. E.
Affiliations
  • California Institute of Technology (US)
  • University of California, Irvine (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Rothbächer, Ute
  • Fraser, Scott E.
Venue
The EMBO Journal
Published
2000-03-01
Volume
19
Issue
5
Pages
1010-1022
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W2149429346
Cited by
299
References
66
Citations by year
2026: 4 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 7 · 2013: 9 · 2012: 17
FWCI
6.02
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders
  • Boehringer Ingelheim Fonds
  • National Institutes of Health (5r01hd025390-09, 5p50mh049176-10)
  • National Institute of Mental Health (MH49176)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-29507, R01HD029507, HD25390)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
Keywords
Dishevelled, Frizzled receptors, dorsoventral patterning, protein phosphorylation, membrane translocation, subcellular localization, DIX domain, DEP domain, protein oligomerization, Wnt signaling, Xenopus embryo
MeSH terms
Dishevelled Proteins, Animals, Biological Transport, Embryo, Nonmammalian, Phosphoproteins, Phosphorylation, Xenopus, Gene Expression Regulation, Developmental, Insect Proteins, Xenopus Proteins, Adaptor Proteins, Signal Transducing

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