The canonical Wnt signalling pathway acts by slowing the rate of ubiquitin-mediated β-catenin degradation. This results in the accumulation and subsequent nuclear translocation of β-catenin, which induces the expression of a number of genes involved in growth, differentiation and metabolism. The mechanisms regulating the Wnt signalling pathway in the physiological context is still not fully understood. In the present study we provide evidence that changes in glucose levels within the physiological range can acutely regulate the levels of β-catenin in two macrophage cell lines (J774.2 and RAW264.7 cells). In particular we find that glucose induces these effects by promoting an autocrine activation of Wnt signalling that is mediated by the hexosamine pathway and changes in N-linked glycosylation of proteins. These studies reveal that the Wnt/β-catenin system is a glucose-responsive signalling system and as such is likely to play a role in pathways involved in sensing changes in metabolic status.
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Research Article|
November 12 2008
Glucose induces an autocrine activation of the Wnt/β-catenin pathway in macrophage cell lines
Sasha H. Anagnostou;
Sasha H. Anagnostou
1Department of Molecular Medicine and Pathology and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1142, New Zealand
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Peter R. Shepherd
Peter R. Shepherd
1
1Department of Molecular Medicine and Pathology and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1142, New Zealand
1To whom correspondence should be addressed (email peter.shepherd@auckland.ac.nz).
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Publisher: Portland Press Ltd
Received:
July 15 2008
Revision Received:
September 24 2008
Accepted:
September 30 2008
Accepted Manuscript online:
September 30 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 416 (2): 211–218.
Article history
Received:
July 15 2008
Revision Received:
September 24 2008
Accepted:
September 30 2008
Accepted Manuscript online:
September 30 2008
Citation
Sasha H. Anagnostou, Peter R. Shepherd; Glucose induces an autocrine activation of the Wnt/β-catenin pathway in macrophage cell lines. Biochem J 1 December 2008; 416 (2): 211–218. doi: https://doi.org/10.1042/BJ20081426
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