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 down-regulates the TCF/LEF-related protein, POP-1, to specify posterior cell fates. Effectors of this signaling pathway include a beta-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.
Shin
T H
TH
University of Massachusetts Medical School, Program in Molecular Medicine, Worcester 01605, USA.
Yasuda
J
J
Rocheleau
C E
CE
Lin
R
R
Soto
M
M
Bei
Y
Y
Davis
R J
RJ
Mello
C C
CC
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000502:physiology*; D004707:Endoderm / Q000502:physiology; D004789:Enzyme Activation; D015801:Helminth Proteins / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D015801:Helminth Proteins; D006609:High Mobility Group Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; C120104:WRM-1 protein, C elegans; C120084:mom-4 protein, C elegans; C096787:pop-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C120085:lit-1 protein, C elegans