PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling.
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.
Sun
T Q
TQ
Cardiovascular Research Institute, University of California, San Francisco, California, USA.
Lu
B
B
Feng
J J
JJ
Reinhard
C
C
Jan
Y N
YN
Fantl
W J
WJ
Williams
L T
LT
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D029742:Caenorhabditis elegans Proteins; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000187:drug effects; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000196:embryology; D029721:Drosophila Proteins; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects; D008934:Mitogens / Q000502:physiology; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000494:pharmacology / Q000502:physiology*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D008934:Mitogens; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C000606588:dsh protein, Drosophila; C409406:PAR-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases