The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Phosphorylation by Glycogen Synthase Kinase-3β Down-regulates Notch Activity, a Link for Notch and Wnt Pathways
Open accessAbstract
Phosphorylation of Notch proteins has been indirectly correlated with Notch activation and nuclear translocation as well as cellular transformation. There is evidence that the Wnt signaling pathway, which results in glycogen synthase kinase-3 beta (GSK-3 beta) inhibition, cross-talks with the Notch pathway. In this study, we show that GSK-3 beta is able to bind and phosphorylate Notch2 in vitro and in vivo. We identify three specific phosphorylation sites in the Notch2 serine/threonine-rich domain that are dependent on GSK-3 beta activity. Phosphorylation of the serine/threonine-rich domain has been shown previously to be crucial in regulating cytokine-specific cell differentiation. Coimmunoprecipitation experiments show that full-length Notch2 binds more efficiently than intracellular Notch2 to GSK-3 beta. Nevertheless, only the processed Notch2 is a substrate for the kinase, thus suggesting that GSK-3 beta-dependent phosphorylation may be specifically regulating the activated Notch molecule. Consistent with this, GSK-3 beta inhibits the transcriptional activation of Notch target genes both in vitro and in vivo, whereas lithium chloride treatment or Wnt-1 overexpression that results in GSK-3 beta inhibition leads to the up-regulation of the Hes-1 promoter. Together, our results suggest that cross-talk between Notch and Wnt pathways may be partially mediated by specific regulation of GSK-3 beta-dependent Notch phosphorylation.
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Cites
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Cited by
Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update
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Notch signaling: simplicity in design, versatility in function
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Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance
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Metadata
- Authors
- Espinosa, L., Inglés-Esteve, J., Aguilera, C., & Bigas, A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 278
- Issue
- 34
- Pages
- 32227-32235
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1990879144
- Cited by
- 337
- References
- 43
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Espinosa, L., Inglés-Esteve, J., Aguilera, C., & Bigas, A. (2003). Phosphorylation by Glycogen Synthase Kinase-3β Down-regulates Notch Activity, a Link for Notch and Wnt Pathways. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m304001200
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