Cited by 2,257Wnt/β-catenin signaling in development and cancerHedgehog Signaling Pathway StudiesDevelopmental Biology and Gene Regulation

Wnt proteins are lipid-modified and can act as stem cell growth factors

Willert, Karl, Brown, Jeffrey D., Danenberg, Esther, Duncan, Andrew W., Weissman, Irving L., Reya, Tannishtha, Yates, John R., Nusse, Roel·2003·Nature

Abstract

Wnt signalling is involved in numerous events in animal development, including the proliferation of stem cells and the specification of the neural crest. Wnt proteins are potentially important reagents in expanding specific cell types, but in contrast to other developmental signalling molecules such as hedgehog proteins and the bone morphogenetic proteins, Wnt proteins have never been isolated in an active form. Although Wnt proteins are secreted from cells, secretion is usually inefficient and previous attempts to characterize Wnt proteins have been hampered by their high degree of insolubility. Here we have isolated active Wnt molecules, including the product of the mouse Wnt3a gene. By mass spectrometry, we found the proteins to be palmitoylated on a conserved cysteine. Enzymatic removal of the palmitate or site-directed and natural mutations of the modified cysteine result in loss of activity, and indicate that the lipid is important for signalling. The purified Wnt3a protein induces self-renewal of haematopoietic stem cells, signifying its potential use in tissue engineering.

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Crossref · 10.1038/nature01611

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  • The Wnt proteins are glycosylated in the endoplasmic reticulum and also are palmitolated.

    “Studies have revealed that the Wnt proteins are glycosylated in the endoplasmic reticulum and also are palmitolated.9,10”

    From Wnt signal transduction pathways (2008) · cites this paper as [10]

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Authors
Willert, K., Brown, J. D., Danenberg, E., Duncan, A. W., Weissman, I. L., Reya, T., Yates, J. R., & Nusse, R.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Duke University (US)
  • Stanford Medicine (US)
  • Scripps Research Institute (US)
Venue
Nature
Published
2003-04-27
Volume
423
Issue
6938
Pages
448-452
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2147864074
Cited by
2,257
References
30
Citations by year
2026: 40 · 2025: 42 · 2024: 48 · 2023: 54 · 2022: 63 · 2021: 63 · 2020: 78 · 2019: 87 · 2018: 86 · 2017: 90 · 2016: 100 · 2015: 101 · 2014: 99 · 2013: 106 · 2012: 133
FWCI
48.13
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067834)
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 › Hedgehog Signaling Pathway Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
Wnt proteins, Wnt3a, palmitoylation, lipid modification, cysteine modification, Wnt signaling, hematopoietic stem cells, stem cell self-renewal, stem cell growth factor, tissue engineering, neural crest specification, protein purification
MeSH terms
Amino Acid Sequence, Animals, Cell Differentiation, Cell Division, Cysteine, Cytoskeletal Proteins, Drosophila melanogaster, Growth Substances, Hematopoietic Stem Cells, L Cells, Molecular Sequence Data, Palmitic Acids, Proteins, Solubility, Xenopus laevis, Signal Transduction, Trans-Activators, Mutagenesis, Site-Directed, Conserved Sequence, Hematopoietic Stem Cell Transplantation, Xenopus Proteins, Zebrafish Proteins, Lipid Metabolism, Wnt Proteins, beta Catenin, Mice, Wnt3 Protein, Wnt3A Protein

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