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

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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

DOI 10.1093/emboj/19.5.1010PMC PMC305640

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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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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.
ORCID: Rothbächer, Ute
Deardorff, Matthew A.
Klein, Peter S.
Cho, Ken W.Y.
Fraser, Scott E.
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2000-03-01
Volume: 19
Issue: 5
Pages: 1010-1022
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1093/emboj/19.5.1010
PMC: PMC305640
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: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis

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