Wnt/β-catenin signaling: components, mechanisms, and diseases

By Bryan T. MacDonald, K. Tamai, Xi He. 2009

5,432 citations recorded by the source corpus.

Signaling by the Wnt family of secreted glycolipoproteins via the transcription co-activator β-catenin controls embryonic development and adult homeostasis. Here we review recent progresses in this so-called canonical Wnt signaling pathway. We discuss Wnt ligands, agonists and antagonists and their interactions with Wnt receptors. We also dissect critical events that regulate β-catenin stability from Wnt receptors to the cytoplasmic β-catenin destruction complex, and nuclear machinery that mediates β-catenin-dependent transcription. Finally we highlight some key aspects of Wnt/β-catenin signaling in human diseases including congenital malformations, cancer and osteoporosis and potential therapeutic implications.

Subfields: Molecular Biology

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Citations in the corpus

Precise Regulation of Porcupine Activity Is Required for Physiological Wnt Signaling (2012, background): “Multiple Wnttriggered pathways coordinately regulate key developmental processes as well as adult tissue homeostasis and repair, and are dysregulated in diverse diseases including cancer, malformation syndromes, osteoporosis, diabetic retinopathy, and pulmonary fibrosis (1-5).”
Wnt Signaling Requires the Sequestration of Glycogen Synthase Kinase 3 inside Multivesicular Endosomes (2010, background): “GSK3 phosphorylation of LRP6 initiates Wnt signaling (MacDonald et al., 2009; Niehrs and Shen, 2010), yet genetic and pharmacological studies show that GSK3 inhibition is sufficient to trigger the canonical Wnt signal (Logan and Nusse, 2004).”
Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases (2014, neutral): “Activation of Wnt signaling disrupts the complex (not shown), blocking phosphorylation of β-catenin by GSK3, resulting in β-catenin stabilization (MacDonald et al., 2009; Valvezan and Klein, 2012; Willert and Nusse, 2012).”
Fibroblasts: origins, definitions, and functions in health and disease (2021, background): “Upon ligand binding, the destruction complex is dissembled, leading to cytoplasmic b-catenin stabilization and translocation to the nucleus, where it forms complexes with transcription factors of the TCF/LEF family to regulate downstream gene expression (MacDonald et al., 2009).”
Alternative Wnt Signaling Activates YAP/TAZ (2015, background): “Canonical Wnt signaling acts through b-catenin/ TCF transcriptional activity (referred to as ‘‘Wnt/b-catenin signaling’’) (Logan and Nusse, 2004; MacDonald et al., 2009).”
Brassinosteroid signal transduction from receptor kinases to transcription factors. (2010, background): “In mammals, GSK3β action is modulated by phosphorylation in its N-terminal domain, protein complex formation, and by priming phosphorylation of its substrate (54).”
Critical roles of SMYD2-mediated β-catenin methylation for nuclear translocation and activation of Wnt signaling (2017, background): “β-catenin functions as the transcriptional co-activator in the Wnt signaling pathway and transmits the signal by regulating the downstream genes including key developmental genes or those involved in development/progression of human cancer [1-5].”
Notum is required for neural and head induction via Wnt deacylation, oxidation and inactivation (2015, neutral): “TheWnt family of secreted lipoproteins controls animal development including axial patterning and cell fate specification and governs tissue homeostasis and stem cell renewal (Clevers and Nusse, 2012; MacDonald et al., 2009).”