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