ArticleThe Journal of biological chemistry2014
Tyrosine-based signal mediates LRP6 receptor endocytosis and desensitization of Wnt/β-catenin pathway signaling.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Serine/threonine/tyrosine kinase 1 drives pancreatic carcinogenesis via GSK3β sequestration-mediated Wnt/β-catenin pathway hyperactivation.Signal transduction and targeted therapy · 2025Article
- Wnt signalosome assembly is governed by conformational flexibility of Axin and by the AP2 clathrin adaptor.Nature communications · 2025Article
- Aberrant Wnt/β-catenin signaling in the mesenchymal stem cells of LZTFL1-depleted mice leads to increased adipogenesis, with implications for obesity.The Journal of biological chemistry · 2025Article
- P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker.Oncogenesis · 2024Article
- SNX9 family mediates βarrestin-independent GPCR endocytosis.Communications biology · 2024Article
- Wnt7a Decreases Brain Endothelial Barrier Function Via β-Catenin Activation.Molecular neurobiology · 2024Article
- EGFR-dependent endocytosis of Wnt9a and Fzd9b promotes β-catenin signaling during hematopoietic stem cell development in zebrafish.Science signaling · 2024Article
- Wnt/β-catenin signaling: Structure, assembly and endocytosis of the signalosome.Development, growth & differentiation · 2021Review
- Regulation of Wnt Signaling Pathways at the Plasma Membrane and Their Misregulation in Cancer.Frontiers in cell and developmental biology · 2021Review
- LRPs in WNT Signalling.Handbook of experimental pharmacology · 2021Review
- Downregulation of beta-catenin in chemo-tolerant TNBC through changes in receptor and antagonist profiles of the WNT pathway: Clinical and prognostic implications.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- β-catenin-mediated Wnt signal transduction proceeds through an endocytosis-independent mechanism.Molecular biology of the cell · 2020Article
- Membrane capacitance recordings resolve dynamics and complexity of receptor-mediated endocytosis in Wnt signalling.Scientific reports · 2019Article
- A Role for the WNT Co-Receptor LRP6 in Pathogenesis and Therapy of Epithelial Cancers.Cancers · 2019Review
- USP9X Deubiquitylates DVL2 to Regulate WNT Pathway Specification.Cell reports · 2019Article
- Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress.International journal of molecular sciences · 2019Article
- WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop.Cell reports · 2019Article
- Antigen B from Echinococcus granulosus enters mammalian cells by endocytic pathways.PLoS neglected tropical diseases · 2018Article
- The function of endocytosis in Wnt signaling.Cellular and molecular life sciences : CMLS · 2018Review
- The Membrane Glycoprotein M6a Endocytic/Recycling Pathway Involves Clathrin-Mediated Endocytosis and Affects Neuronal Synapses.Frontiers in molecular neuroscience · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Wnt/β-catenin signaling orchestrates a number of critical events including cell growth, differentiation, and cell survival during development. Misregulation of this pathway leads to various human diseases, specifically cancers. Endocytosis and phosphorylation of the LDL receptor-related protein 6 (LRP6), an essential co-receptor for Wnt/β-catenin signaling, play a vital role in mediating Wnt/β-catenin signal transduction. However, its regulatory mechanism is not fully understood. In this study, we define the mechanisms by which LRP6 endocytic trafficking regulates Wnt/β-catenin signaling activation. We show that LRP6 mutant with defective tyrosine-based signal in its cytoplasmic tail has an increased cell surface distribution and decreased endocytosis rate. These changes in LRP6 endocytosis coincide with an increased distribution to caveolae, increased phosphorylation, and enhanced Wnt/β-catenin signaling. We further demonstrate that treatment of Wnt3a ligands or blocking the clathrin-mediated endocytosis of LRP6 leads to a redistribution of wild-type receptor to lipid rafts. The LRP6 tyrosine mutant also exhibited an increase in signaling activation in response to Wnt3a stimulation when compared with wild-type LRP6, and this activation is suppressed when caveolae-mediated endocytosis is blocked. Our results reveal molecular mechanisms by which LRP6 endocytosis routes regulate its phosphorylation and the strength of Wnt/β-catenin signaling, and have implications on how this pathway can be modulated in human diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.