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Wnt activates the Tak1/Nemo-like kinase pathway
Linda Smit1, Annette Baas, Jeroen Kuipers
1Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
The Journal of Biological Chemistry
|February 13, 2004
Summary
Wnt signaling directly activates the MOM-4/Tak1 pathway, influencing endoderm-mesoderm specification. This Wnt-induced Tak1 activation phosphorylates TCF, potentially acting as a feedback mechanism.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Biology
Background:
- Wnt and MAPK pathways are crucial for endoderm-mesoderm specification in C. elegans.
- A proposed model suggests Tak1 kinase cascade counteracts Wnt cascade via TCF phosphorylation.
- The specific signal activating the Tak1 cascade remained unknown.
Purpose of the Study:
- To investigate whether Wnt directly activates the Tak1 kinase cascade.
- To elucidate the mechanism of Wnt signal transduction in endoderm-mesoderm specification.
Main Methods:
- Utilized genetic studies in Caenorhabditis elegans.
- Stimulated cells with Wnt1 and analyzed MOM-4/Tak1 activation.
- Investigated the role of TAP-1/Tab1 adaptor protein.
Main Results:
- Wnt1 stimulation leads to MOM-4/Tak1 autophosphorylation and activation, dependent on TAP-1/Tab1.
- Wnt1-induced Tak1 activation phosphorylates LIT-1/Nemo-like kinase.
- TCF phosphorylation was observed following Wnt1-induced Tak1 activation.
Conclusions:
- Wnt directly activates the MOM-4/Tak1 kinase signaling pathway.
- Wnt activates beta-catenin/TCF via the canonical pathway.
- Wnt activates the Tak1 pathway to phosphorylate and inhibit TCF, suggesting a feedback loop.