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Differential Regulation of Glycogen Synthase Kinase 3β by Insulin and Wnt Signaling
Open accessAbstract
Glycogen synthase kinase 3beta (GSK3beta) is a key component in many biological processes including insulin and Wnt signaling. Since the activation of each signaling pathway results in a decrease in GSK3beta activity, we examined the specificity of their downstream effects in the same cell type. Insulin induces an increased activity of glycogen synthase but has no influence on the protein level of beta-catenin. In contrast, Wnt increases the cytosolic pool of beta-catenin but not glycogen synthase activity. We found that, unlike insulin, neither the phosphorylation status of the serine9 residue of GSK3beta nor the activity of protein kinase B is regulated by Wnt. Although the decrease in GSK3beta activity is required, GSK3beta may not be the limiting component for Wnt signaling in the cells that we examined. Our results suggest that the axin-conductin complexed GSK3beta may be dedicated to Wnt rather than insulin signaling. Insulin and Wnt pathways regulate GSK3beta through different mechanisms, and therefore lead to distinct downstream events.
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Cites
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Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells
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Increasing complexity of Ras signaling
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Casein kinase I transduces Wnt signals
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Cited by
GSK-3: tricks of the trade for a multi-tasking kinase
Doble, B. W., & Woodgett, J. R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00384 · Cited by 2,084
Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase Mechanism
Liu, C., Li, Y., Semenov, M., Han, C., Baeg, G.-H., Tan, Y., Zhang, Z., Lin, X., & He, X. (2002) · Cell · doi:10.1016/s0092-8674(02)00685-2 · Cited by 2,069
The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation
Mendoza, M. C., Er, E. E., & Blenis, J. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.03.006 · Cited by 1,817
The many faces and functions of β‐catenin
Valenta, T., Hausmann, G., & Basler, K. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.150 · Cited by 1,598
GSK3 takes centre stage more than 20 years after its discovery
FRAME, S., & COHEN, P. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3590001 · Cited by 1,433
Metadata
- Authors
- Ding, V. W., Chen, R.-H., & McCormick, F.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 275
- Issue
- 42
- Pages
- 32475-32481
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2022309233
- Cited by
- 427
- References
- 6
- FWCI
- 7.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
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