Distinct PAR-1 Proteins Function in Different Branches of Wnt Signaling during Vertebrate Development
Open accessAbstract
The kinase PAR-1 plays conserved roles in cell polarity. PAR-1 has also been implicated in axis establishment in C. elegans and Drosophila and in Wnt signaling, but its role in vertebrate development is unclear. Here we report that PAR-1 has two distinct and essential roles in axial development in Xenopus mediated by different PAR-1 isoforms. Depletion of PAR-1A or PAR-1BX causes dorsoanterior deficits, reduced Spemann organizer gene expression, and inhibition of canonical Wnt-beta-catenin signaling. By contrast, PAR-1BY depletion inhibits cell movements and localization of Dishevelled protein to the cell cortex, processes associated with noncanonical Wnt signaling. PAR-1 phosphorylation sites in Dishevelled are required for this translocation, but not for canonical Wnt signaling. We conclude that PAR-1BY is required in the PCP branch and mediates Dsh membrane localization while PAR-1A and PAR-1BX are essential for canonical signaling to beta-catenin, possibly via targets other than Dishevelled.
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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 [41]
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- Authors
- Ossipova, O., Dhawan, S., Sokol, S., & Green, J. B. A.
- Affiliations
- Harvard University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Green, Jeremy B.A.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 8
- Issue
- 6
- Pages
- 829-841
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2008911576
- Cited by
- 113
- References
- 76
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 4 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 7 · 2014: 8 · 2013: 6 · 2012: 8
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- 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 › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Keywords
- protease-activated receptor 1, Wnt signaling, canonical Wnt/β-catenin pathway, non-canonical Wnt signaling, planar cell polarity, Dishevelled, Spemann organizer, Xenopus, cell polarity, cell motility, protein phosphorylation
- MeSH terms
- Animals, Autoradiography, Cell Membrane, Cytoskeletal Proteins, Dose-Response Relationship, Drug, Enzyme Activation, Luciferases, Microinjections, Phenotype, Phosphorylation, RNA, Protein Biosynthesis, Xenopus, Xenopus laevis, Blotting, Western, Signal Transduction, Trans-Activators, Oligonucleotides, Antisense, Protein Serine-Threonine Kinases, In Situ Hybridization, Gene Expression Regulation, Developmental, Body Patterning, Protein Isoforms, Xenopus Proteins, Animals, Genetically Modified, Intercellular Signaling Peptides and Proteins, Tissue Culture Techniques, JNK Mitogen-Activated Protein Kinases, Green Fluorescent Proteins, Wnt Proteins, beta Catenin
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