PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling

Wnt signalling regulates beta -catenin-dependent developmental processes th rough the Dishevelled protein (Dsh), Dsh regulates two distinct pathways, o ne mediated by beta -catenin and the other by Jun kinase (JNK), We have pur ified a Dsh-associated kinase from Drosophila that encodes a homologue of C aenorhabditis elegans PAR-I, a known determinant of polarity during asymmet ric cell divisions. Treating cells with Wnt increases endogenous PAR-I acti vity coincident with Dsh phosphorylation, PAR-1 potentiates Wnt activation of the beta -catenin pathway but blocks the JNK pathway. Suppressing endoge nous PAR-1 function inhibits Wnt signalling through beta -catenin in mammal ian 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 modula tor of Wnt-beta -catenin signalling, indicating a link between two importan t developmental pathways.