MOM-4, a MAP Kinase Kinase Kinase–Related Protein, Activates WRM-1/LIT-1 Kinase to Transduce Anterior/Posterior Polarity Signals in C. elegans
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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.
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Mutations in lit-1 or mom-4 cause a loss of polarity and POP-1 asymmetry.
“Mutations in lit-1 or mom-4 cause a loss of polarity and POP-1 asymmetry (16, 22, 27).”
The mom-4 gene encodes a MAPK kinase kinase-like protein related to the mammalian protein kinase TAK1.
“The mom-4 gene encodes a MAPK kinase kinase-like protein related to the mammalian protein kinase TAK1.”
MOM-4 can activate kinase activity of the LIT-1-WRM-1 complex.
“Furthermore, MOM-4 can activate kinase activity of the LIT-1-WRM-1 complex (27).”
The lit-1 gene encodes a MAPK-like protein similar to the Drosophila Nemo protein kinase and the mouse Nemo-like kinase (NLK).
“The lit-1 gene encodes a mitogen-activated protein kinase (MAPK)-like protein similar to the Drosophila Nemo protein kinase and the mouse Nemo-like kinase (NLK).”
A MAPK-related pathway acts in concert with Wnt signaling to establish anterior-posterior polarity in C. elegans.
“Thus, a MAPK-related pathway acts in concert with Wnt signaling to establish anterior-posterior polarity in C. elegans.”
Wnt signaling and the MAPK-related cascade both act to control polarity by regulating POP-1, and integration of the two signals occurs at the level of complex formation between WRM-1 and LIT-1.
“These results suggest that Wnt signaling and the MAPK-related cascade both act to control polarity by regulating POP-1 and that integration of two signals occurs at the level of complex formation between WRM-1 and LIT-1.”
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References 29 · Cited by 123
- Authors
- Shin, T. H., Yasuda, J., Rocheleau, C. E., Lin, R., Soto, M., Bei, Y., Davis, R. J., & Mello, C. C.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Howard Hughes Medical Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Mello, Craig C.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 4
- Issue
- 2
- Pages
- 275-280
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2155054751
- Cited by
- 123
- References
- 29
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2017: 2 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 7
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- MAP kinase kinase kinase, anterior-posterior polarity, β-catenin, kinase activation, Caenorhabditis elegans
- MeSH terms
- Amino Acid Sequence, Animals, Cytoskeletal Proteins, DNA-Binding Proteins, Embryo, Nonmammalian, Endoderm, Enzyme Activation, High Mobility Group Proteins, Membrane Proteins, Molecular Sequence Data, Phosphorylation, Transcription Factors, Signal Transduction, Helminth Proteins, Sequence Alignment, Conserved Sequence, Caenorhabditis elegans, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, Body Patterning, Caenorhabditis elegans Proteins
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