Dishevelled 2 Recruits ß-Arrestin 2 to Mediate Wnt5A-Stimulated Endocytosis of Frizzled 4
Abstract
Wnt proteins, regulators of development in many organisms, bind to seven transmembrane–spanning (7TMS) receptors called frizzleds, thereby recruiting the cytoplasmic molecule dishevelled (Dvl) to the plasma membrane.Frizzled-mediated endocytosis of Wg (a Drosophila Wnt protein) and lysosomal degradation may regulate the formation of morphogen gradients. Endocytosis of Frizzled 4 (Fz4) in human embryonic kidney 293 cells was dependent on added Wnt5A protein and was accomplished by the multifunctional adaptor protein β-arrestin 2 (βarr2), which was recruited to Fz4 by binding to phosphorylated Dvl2. These findings provide a previously unrecognized mechanism for receptor recruitment of β-arrestin and demonstrate that Dvl plays an important role in the endocytosis of frizzled, as well as in promoting signaling.
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Dsh is phosphorylated by a number of kinases including Casein Kinase 1, Casein Kinase 2, Metastasis Associated Kinase, Protein Kinase C and Par1.
“Dsh is phosphorylated by a number of kinases including Casein Kinase 1,37 Casein Kinase 2,38 Metastasis Associated Kinase,39 Protein Kinase C40 and Par1.41”
From Wnt signal transduction pathways (2008) · cites this paper as [40]
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- Authors
- Chen, W., ten Berge, D., Brown, J., Ahn, S., Hu, L. A., Miller, W. E., Caron, M. G., Barak, L. S., Nusse, R., & Lefkowitz, R. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
- Corresponding author
- Miller, William E.
- Lefkowitz, Robert J.
- ORCID
- Venue
- Science
- Published
- 2003-09-05
- Volume
- 301
- Issue
- 5638
- Pages
- 1391-1394
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2039435520
- Cited by
- 334
- References
- 22
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 7 · 2018: 14 · 2017: 15 · 2016: 13 · 2015: 11 · 2014: 19 · 2013: 24 · 2012: 22
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl061365-04)
- National Heart, Lung, and Blood Institute (HL 16037, HL61365)
- National Institute of Neurological Disorders and Stroke (NS-19576, R01NS019576)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Dishevelled 2, β-arrestin2, Wnt5a, Frizzled-4, receptor internalization, Wnt signaling, Frizzled receptors, morphogen gradients, G protein-coupled receptor signaling
- MeSH terms
- beta-Arrestins, beta-Arrestin 2, Wnt-5a Protein, Dishevelled Proteins, Animals, Cell Line, Cell Membrane, Clathrin, Cytoplasm, Endocytosis, Humans, Phosphoproteins, Phosphorylation, Protein Kinase C, Proteins, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Signal Transduction, Arrestins, Drosophila Proteins, RNA, Small Interfering, Adaptor Proteins, Signal Transducing, Wnt Proteins, Frizzled Receptors, Mice
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