Role of the TAK1-NLK-STAT3 pathway in TGF-β-mediated mesoderm induction
Open accessAbstract
Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) and Nemo-like kinase (NLK) function in Xenopus, Drosophila, and Caenorhabditis elegans development. Here we report that serine phosphorylation of STAT3 induced by TAK1-NLK cascade is essential for TGF-β-mediated mesoderm induction in Xenopus embryo. Depletion of TAK1, NLK, or STAT3 blocks TGF-β-mediated mesoderm induction. Coexpression of NLK and STAT3 induces mesoderm by a mechanism that requires serine phosphorylation of STAT3. Activin activates NLK, which in turn directly phosphorylates STAT3. Moreover, depletion of either TAK1 or NLK inhibits endogenous serine phosphorylation of STAT3. These results provide the first evidence that TAK1-NLK-STAT3 cascade participates in TGF-β-mediated mesoderm induction.
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Direct binding of NLK to STAT3 results in phosphorylation of STAT3 at Ser727, requiring activity of the TAK1-NLK cascade.
“Direct binding of NLK to STAT3 resulted in phosphorylation of STAT3 at Ser727, which requires the activity of the TAK1-NLK cascade [22,23].”
From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [22]
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Ishitani, T., Ninomiya-Tsuji, J., Nagai, S.-I., Nishita, M., Meneghini, M., Barker, N., Waterman, M., Bowerman, B., Clevers, H., Shibuya, H., et al. (1999) · Nature · doi:10.1038/21674 · Cited by 624 · see citing works
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- Smith, J.C., Conlon, F.L., Saka, Y., and Tada, M. 2000. Xwnt11 and the regulation of gastrulation in Xenopus. Philos. Trans. R Soc. Lond. B 355: 923-930.
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Chakraborty, D., Šumová, B., Mallano, T., Chen, C.-W., Distler, A., Bergmann, C., Ludolph, I., Horch, R. E., Gelse, K., Ramming, A., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01236-6 · Cited by 356 · see citing works
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“…3-kinase (PI3K) (Kim et al., 2009) and Ras proteins (Saitoh et al., 2016); and 3) cell type (Boulton et al., 1995; Chung et al., 1997; Jain et al., 1999; Yokogami et al., 2000; Abe et al., 2001; Wierenga et al., 2003; Fu et al., 2004; Ohkawara et al., 2004; Kojima et al., 2005; Sato et al., 2005).”
BackgroundAtypical mitogen-activated protein kinases: Structure, regulation and functions
Coulombe, P., & Meloche, S. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.11.001 · Cited by 298 · see citing works
IL-6-STAT3 signaling and premature senescence
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Nemo‐like kinase is involved in NGF‐induced neurite outgrowth via phosphorylating MAP1B and paxillin
Ishitani, T., Ishitani, S., Matsumoto, K., & Itoh, M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06400.x · Cited by 44 · see citing works
Self-citationNemo-Like Kinase in Development and Diseases: Insights from Mouse Studies
Daams, R., & Massoumi, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239203 · Cited by 21 · see citing works
- Authors
- Ohkawara, B., Shirakabe, K., Hyodo-Miura, J., Matsuo, R., Ueno, N., Matsumoto, K., & Shibuya, H.
- Affiliations
- Tokyo Medical and Dental University (JP)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-02-15
- Volume
- 18
- Issue
- 4
- Pages
- 381-386
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC359392
- OpenAlex
- W2165047377
- Cited by
- 106
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 10
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- TAK1, Nemo-like kinase, STAT3, TGF-beta signaling, mesoderm induction, serine phosphorylation, activin, Xenopus embryo, kinase cascade, embryonic development
- MeSH terms
- Animals, Carrier Proteins, DNA-Binding Proteins, Drosophila, Embryo, Nonmammalian, Mesoderm, Phosphoprotein Phosphatases, Xenopus, Trans-Activators, Transforming Growth Factor beta, Mutagenesis, Site-Directed, Caenorhabditis elegans, Amino Acid Substitution, Mitogen-Activated Protein Kinases, Xenopus Proteins, Intracellular Signaling Peptides and Proteins, STAT3 Transcription Factor
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