GSK-3: tricks of the trade for a multi-tasking kinase
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- Teacher spread
- 0.286 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine kinase found in all eukaryotes. The enzyme is a key regulator of numerous signalling pathways, including cellular responses to Wnt, receptor tyrosine kinases and G-protein-coupled receptors and is involved in a wide range of cellular processes, ranging from glycogen metabolism to cell cycle regulation and proliferation. GSK-3 is unusual in that it is normally active in cells and is primarily regulated through inhibition of its activity. Another peculiarity compared with other protein kinases is its preference for primed substrates, that is, substrates previously phosphorylated by another kinase. Several recent advances have improved our understanding of GSK-3 regulation in multiple pathways. These include the solution of the crystal structure of GSK-3, which has provided insight into GSK-3's penchant for primed substrates and the regulation of GSK-3 by serine phosphorylation, and findings related to the involvement of GSK-3 in the Wnt/beta-catenin and Hedgehog pathways. Finally, since increased GSK-3 activity may be linked to pathology in diseases such as Alzheimer's disease and non-insulin-dependent diabetes mellitus, several new GSK-3 inhibitors, such as the aloisines, the paullones and the maleimides, have been developed. Although they are just starting to be characterized in cell culture experiments, these new inhibitors hold promise as therapeutic agents.
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The record
- Venue
- Journal of Cell Science
- Topic
- Wnt/β-catenin signaling in development and cancer
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Ontario Institute for Cancer Research
- Funders
- Canadian Institutes of Health Research
- Keywords
- GSK-3BiologyWnt signaling pathwayKinaseCell biologyGlycogen synthaseHedgehogProtein-Serine-Threonine KinasesProtein kinase APhosphorylationGSK3BBiochemistrySignal transduction
- Has abstract in OpenAlex
- yes