Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Animals, Genetically Modified
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Autoradiography / methods
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Blotting, Western / methods
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Body Patterning / physiology
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Cytoskeletal Proteins / metabolism
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Dose-Response Relationship, Drug
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Gene Expression Regulation, Developmental* / drug effects
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Green Fluorescent Proteins / metabolism
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In Situ Hybridization / methods
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Intercellular Signaling Peptides and Proteins / metabolism*
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JNK Mitogen-Activated Protein Kinases
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Luciferases / metabolism
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Microinjections / methods
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Oligonucleotides, Antisense / pharmacology
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Phenotype
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Phosphorylation
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / physiology
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Protein Isoforms / metabolism
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / deficiency
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Protein Serine-Threonine Kinases / physiology*
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RNA / chemical synthesis
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Tissue Culture Techniques
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Trans-Activators / metabolism
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Wnt Proteins
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Xenopus
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Xenopus Proteins / chemistry
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Xenopus Proteins / deficiency
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Xenopus Proteins / physiology*
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Xenopus laevis / embryology*
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Xenopus laevis / genetics
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Xenopus laevis / metabolism*
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beta Catenin
Substances
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CTNNB1 protein, Xenopus
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Cytoskeletal Proteins
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Intercellular Signaling Peptides and Proteins
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Oligonucleotides, Antisense
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Protein Isoforms
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Trans-Activators
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Wnt Proteins
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Xenopus Proteins
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beta Catenin
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Green Fluorescent Proteins
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RNA
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Luciferases
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MARK3 protein, Xenopus
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Protein Serine-Threonine Kinases
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JNK Mitogen-Activated Protein Kinases