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-I, a known determinant of polarity during asymmetric cell divisions. Treating cells with Wnt increases endogenous PAR-I 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-I, a regulator of polarity, is also a modulator of Wnt-beta -catenin signalling, indicating a link between two important developmental pathways.