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

Author

Listed:
  • Karl Willert

    (Stanford University School of Medicine)

  • Jeffrey D. Brown

    (Stanford University School of Medicine)

  • Esther Danenberg

    (Stanford University School of Medicine)

  • Andrew W. Duncan

    (Duke University Medical Center)

  • Irving L. Weissman

    (Stanford University School of Medicine)

  • Tannishtha Reya

    (Duke University Medical Center)

  • John R. Yates

    (The Scripps Research Institute)

  • Roel Nusse

    (Stanford University School of Medicine)

Abstract

Wnt signalling is involved in numerous events in animal development1, including the proliferation of stem cells2 and the specification of the neural crest3. 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 cells4,5,6,7, secretion is usually inefficient8 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.

Suggested Citation

  • Karl Willert & Jeffrey D. Brown & Esther Danenberg & Andrew W. Duncan & Irving L. Weissman & Tannishtha Reya & John R. Yates & Roel Nusse, 2003. "Wnt proteins are lipid-modified and can act as stem cell growth factors," Nature, Nature, vol. 423(6938), pages 448-452, May.
    • Handle: RePEc:nat:nature:v:423:y:2003:i:6938:d:10.1038_nature01611
    DOI: 10.1038/nature01611
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    Cited by:

    1. Cezanne Miete & Gonzalo P. Solis & Alexey Koval & Martina Brückner & Vladimir L. Katanaev & Jürgen Behrens & Dominic B. Bernkopf, 2022. "Gαi2-induced conductin/axin2 condensates inhibit Wnt/β-catenin signaling and suppress cancer growth," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Cummings, F.W, 2004. "A model of morphogenesis," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 339(3), pages 531-547.

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