MOM-4, a MAP Kinase Kinase Kinase–Related Protein, Activates WRM-1/LIT-1 Kinase to Transduce Anterior/Posterior Polarity Signals in C. elegans

In C. elegans, a Wnt/WG-like signaling pathway downregulates the TCF/LEF-related protein, POP-1, to specify posterior cell fates. Effectors of this signaling pathway include a β-catenin homolog, WRM-1, and a conserved protein kinase, LIT-1. WRM-1 and LIT-1 form a kinase complex that can directly phosphorylate POP-1, but how signaling activates WRM-1/LIT-1 kinase is not yet known. Here we show that mom-4, a genetically defined effector of polarity signaling, encodes a MAP kinase kinase kinase–related protein that stimulates the WRM-1/LIT-1-dependent phosphorylation of POP-1. LIT-1 kinase activity requires a conserved residue analogous to an activating phosphorylation site in other kinases, including MAP kinases. These findings suggest that anterior/posterior polarity signaling in C. elegans may involve a MAP kinase–like signaling mechanism.