Nature Cell Biology
3, 628 - 636 (2001)
Published online: 6 June 2001; | doi:10.1038/35083016
PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signallingTian-Qiang Sun1, 2, Bingwei Lu3, Jia-Jia Feng2, Christoph Reinhard2, Yuh Nung Jan3, Wendy J. Fantl2
& Lewis T. Williams1, 21
Cardiovascular Research Institute, University of California, San Francisco, California, USA
2
Chiron Corporation, 4560 Horton Street, 4.6, Emeryville, California 94608, USA
3
Howard Hughes Medical Institute, Department of Physiology and Biochemistry, University of California, San Francisco, California 94143-0725, USA
Correspondence should be addressed to Lewis T. Williams rusty_williams@cc.chiron.comWnt signalling regulates  -catenin-dependent developmental processes through the Dishevelled protein (Dsh). Dsh regulates two distinct pathways, one mediated by -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 -catenin pathway but blocks the JNK pathway. Suppressing endogenous PAR-1 function inhibits Wnt signalling through -catenin in mammalian cells, and Xenopus and Drosophila embryos. PAR-1 seems to be a positive regulator of the -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−-catenin signalling, indicating a link between two important developmental pathways.
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