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-re lated protein, POP-1, to specify posterior cell fates. Effecters of this si gnaling pathway include a beta-catenin homolog, WRM-1, and a conserved prot ein 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 polar ity signaling, encodes a MAP kinase kinase kinase-related protein that stim ulates the WRM-1/LIT-1-dependent phosphorylation of POP-1. LIT-1 kinase act ivity requires a conserved residue analogous to an activating phosphorylati on site in other kinases, including MAP kinases. These findings suggest tha t anterior/posterior polarity signaling in C. elegans may involve a MAP kin ase-like signaling mechanism.