Abstract
Wnt signalling regulates beta-catenin-dependent developmental processes through the Dishevelled protein (Dsh). Dsh regulates two distinct pathways, one mediated by beta-catenin and the other by Jun kinase (JNK). We have purified a Dsh-associated kinase from Drosophila that encodes a homologue of Caenorhabditis elegans PAR-1, a known determinant of polarity during asymmetric cell divisions. Treating cells with Wnt increases endogenous PAR-1 activity coincident with Dsh phosphorylation. PAR-1 potentiates Wnt activation of the beta-catenin pathway but blocks the JNK pathway. Suppressing endogenous PAR-1 function inhibits Wnt signalling through beta-catenin in mammalian cells, and Xenopus and Drosophila embryos. PAR-1 seems to be a positive regulator of the beta-catenin pathway and an inhibitor of the JNK pathway. These findings show that PAR-1, a regulator of polarity, is also a modulator of Wnt-beta-catenin signalling, indicating a link between two important developmental pathways.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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CHO Cells
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Caenorhabditis elegans Proteins*
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Cricetinae
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Cytoskeletal Proteins / drug effects
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Dishevelled Proteins
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Drosophila / embryology
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Drosophila Proteins
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Humans
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases / drug effects
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Mitogens / physiology
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Molecular Sequence Data
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Phosphoproteins / metabolism*
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Phosphorylation
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Protein Binding
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Protein Serine-Threonine Kinases / metabolism
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Protein Serine-Threonine Kinases / pharmacology
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Protein Serine-Threonine Kinases / physiology*
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Proto-Oncogene Proteins / drug effects
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Proto-Oncogene Proteins / pharmacology
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Proto-Oncogene Proteins / physiology*
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Sequence Alignment
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Signal Transduction / drug effects
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Trans-Activators*
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Transcriptional Activation / drug effects
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Tumor Cells, Cultured
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Wnt Proteins
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Xenopus
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Xenopus Proteins
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Zebrafish Proteins*
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beta Catenin
Substances
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Adaptor Proteins, Signal Transducing
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CTNNB1 protein, Xenopus
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CTNNB1 protein, human
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Caenorhabditis elegans Proteins
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Cytoskeletal Proteins
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DVL1 protein, Xenopus
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Dishevelled Proteins
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Drosophila Proteins
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Mitogens
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Phosphoproteins
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Proto-Oncogene Proteins
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Trans-Activators
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Wnt Proteins
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Xenopus Proteins
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Zebrafish Proteins
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beta Catenin
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dsh protein, Drosophila
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PAR-1 protein, C elegans
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Protein Serine-Threonine Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases