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

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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

DOI 10.1038/nature01611

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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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Self-citation
Insulin-Like Growth Factor-Binding Protein 2 Secreted by a Tumorigenic Cell Line Supports Ex Vivo Expansion of Mouse Hematopoietic Stem Cells
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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)
ORCID: Willert, Karl
Danenberg, Esther
Duncan, Andrew W.
Weissman, Irving L.
Reya, Tannishtha
Yates, John R.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2003-04-27
Volume: 423
Issue: 6938
Pages: 448-452
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature01611
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
Licence: www.springer.com/tdm (tdm)
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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Wnt proteins are lipid-modified and can act as stem cell growth factors

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