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Volume 162, Issue 5
1 September 2003
Journal of Cell Biology Cover Image for Volume 162, Issue 5
Article Contents
Article| September 02 2003

Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3–independent β-catenin degradation

Lilia Topol,
Lilia Topol
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
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Xueyuan Jiang,
Xueyuan Jiang
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
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Hosoon Choi,
Hosoon Choi
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
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Lisa Garrett-Beal,
Lisa Garrett-Beal
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
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Peter J. Carolan,
Peter J. Carolan
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
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Yingzi Yang
Yingzi Yang
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
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Author and Article Information
Lilia Topol
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
Xueyuan Jiang
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
Hosoon Choi
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
Lisa Garrett-Beal
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
Peter J. Carolan
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
Yingzi Yang
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
Address correspondence to Yingzi Yang, Genetic Disease Research Branch, National Human Genome Research Institute, NIH, 49 Convent Dr., Room 4A68, Bethesda, MD 20892. Tel: (301) 402-2034. Fax: (301) 402-2170. email: [email protected]

Xueyuan Jiang's present address is Dept. of Biochemistry and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.

Abbreviations used in this paper: AER, apical ectodermal ridge; CEF, chick embryonic fibroblast; CsA, Cyclosporin A.

Received: March 25 2003
Accepted: June 23 2003
Online ISSN: 1540-8140
Print ISSN: 0021-9525
2003
J Cell Biol (2003) 162 (5): 899–908.
https://doi.org/10.1083/jcb.200303158
Article history
Received:
March 25 2003
Accepted:
June 23 2003

Wnts are secreted signaling molecules that can transduce their signals through several different pathways. Wnt-5a is considered a noncanonical Wnt as it does not signal by stabilizing β-catenin in many biological systems. We have uncovered a new noncanonical pathway through which Wnt-5a antagonizes the canonical Wnt pathway by promoting the degradation of β-catenin. This pathway is Siah2 and APC dependent, but GSK-3 and β-TrCP independent. Furthermore, we provide evidence that Wnt-5a also acts in vivo to promote β-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation.

2003
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