ArticleCell systems2020
The Scaffold Protein Axin Promotes Signaling Specificity within the Wnt Pathway by Suppressing Competing Kinase Reactions.
Article in Cell systems, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Unraveling the Clinical and Genetic Landscape of Talipes Equinovarus (Clubfoot).Molecular syndromology · 2026Review
- Article
- Exploring the role of cellular plasticity in metabolic dysfunction-associated steatosis and related molecular mechanisms.Journal of translational medicine · 2025Article
- GSK3α negatively regulates GSK3β by decreasing its protein levels and enzymatic activity in mouse embryonic stem cells.Stem cell reports · 2025Article
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Article
- Structural and functional effects of phosphopriming and scaffolding in the kinase GSK-3β.Science signaling · 2024Article
- Review
- A small molecule compound 759 inhibits the wnt/beta-catenin signaling pathway via increasing the Axin protein stability.Medical oncology (Northwood, London, England) · 2024Article
- Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota.Engineering (Beijing, China) · 2024Article
- Mechanisms of the Wnt Pathways as a Potential Target Pathway in Atherosclerosis.Journal of lipid and atherosclerosis · 2023Review
- Article
- Cabin1 domain-containing gene picd-1 interacts with pry-1/Axin to regulate multiple processes in Caenorhabditis elegans.Scientific reports · 2022Article
- Progressing Vulvar Melanoma Caused by Instability in cKIT Juxtamembrane Domain: A Case Report and Review of Literature.Current oncology (Toronto, Ont.) · 2022Review
- Molecular Insights to the Wnt Signaling During Alzheimer's Disorder: a Potential Target for Therapeutic Interventions.Journal of molecular neuroscience : MN · 2022Review
- The nonredundant nature of the Axin2 regulatory network in the canonical Wnt signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Orchestrating serine/threonine phosphorylation and elucidating downstream effects by short linear motifs.The Biochemical journal · 2022Review
- Reconstitution of the destruction complex defines roles of AXIN polymers and APC in β-catenin capture, phosphorylation, and ubiquitylation.Molecular cell · 2021Article
- Zooming in on the WNT/CTNNB1 Destruction Complex: Functional Mechanistic Details with Implications for Therapeutic Targeting.Handbook of experimental pharmacology · 2021Article
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4 authors.
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Abstract
Scaffold proteins are thought to promote signaling specificity by accelerating reactions between bound kinase and substrate proteins. To test the long-standing hypothesis that the scaffold protein Axin accelerates glycogen synthase kinase 3β (GSK3β)-mediated phosphorylation of β-catenin in the Wnt signaling network, we measured GSK3β reaction rates with multiple substrates in a minimal, biochemically reconstituted system. We observed an unexpectedly small, ∼2-fold Axin-mediated rate increase for the β-catenin reaction when measured in isolation. In contrast, when both β-catenin and non-Wnt pathway substrates are present, Axin accelerates the β-catenin reaction by preventing competition with alternative substrates. At high competitor concentrations, Axin produces >10-fold rate effects. Thus, while Axin alone does not markedly accelerate the β-catenin reaction, in physiological settings where multiple GSK3β substrates are present, Axin may promote signaling specificity by suppressing interactions with competing, non-Wnt pathway targets. This mechanism for scaffold-mediated control of competition enables a shared kinase to perform distinct functions in multiple signaling networks.
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