A Drosophila MAPKKK, D‐MEKK1, mediates stress responses through activation of p38 MAPK
Open accessAbstract
In cultured mammalian cells, the p38 mitogen-activated protein kinase (MAPK) pathway is activated in response to a variety of environmental stresses. How ever, there is little evidence from in vivo studies to demonstrate a role for this pathway in the stress response. We identified a Drosophila MAPK kinase kinase (MAPKKK), D-MEKK1, which can activate p38 MAPK. D-MEKK1 is structurally similar to the mammalian MEKK4/MTK1 MAPKKK. D-MEKK1 kinase activity was activated in animals under conditions of high osmolarity. Drosophila mutants lacking D-MEKK1 were hypersensitive to environmental stresses, including elevated temperature and increased osmolarity. In these D-MEKK1 mutants, activation of Drosophila p38 MAPK in response to stress was poor compared with activation in wild-type animals. These results suggest that D-MEKK1 regulation of the p38 MAPK pathway is critical for the response to environmental stresses in Drosophila.
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Mekk1 is a stress-induced MAP3K that leads to phosphorylation and activation of p38 MAPK.
“Mekk1 is a stress-induced MAP3K that leads to phosphorylation and activation of the stress-activated kinase, p38 MAPK (87).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [87]
Mekk1 is a MAP3K that leads to the phosphorylation and activation of p38/MAPK, which is activated in response to cell stress.
“Mekk1 is a MAP3K that leads to the phosphorylation and activation of p38/MAPK (87), which is activated in response to cell stress (142–144).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [87]
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Research works printed but not linked: 4
- Ashburner,M. (1989) Drosophila, A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
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Seong, K.-H., Li, D., Shimizu, H., Nakamura, R., & Ishii, S. (2011) · Cell · doi:10.1016/j.cell.2011.05.029 · Cited by 322 · see citing works
Bulavin, D. V., Kovalsky, O., Hollander, M. C., & Fornace, A. J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.11.3859-3871.2003 · Cited by 161 · see citing works
Ambegaokar, S. S., & Jackson, G. R. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr432 · Cited by 113 · see citing works
“Mekk1 is a stress-induced MAP3K that leads to phosphorylation and activation of the stress-activated kinase, p38 MAPK (87).”
BackgroundInfluential
- Authors
- Inoue, H., Tateno, M., Fujimura‐Kamada, K., Takaesu, G., Adachi‐Yamada, T., Ninomiya‐Tsuji, J., Irie, K., Nishida, Y., & Matsumoto, K.
- Affiliations
- Nagoya University (JP)
- Corresponding author
- Matsumoto, Kunihiro
- Venue
- The EMBO Journal
- Published
- 2001-10-01
- Volume
- 20
- Issue
- 19
- Pages
- 5421-5430
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC125648
- OpenAlex
- W2054373856
- Cited by
- 99
- References
- 0
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 2 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 4
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Daiko Foundation
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- MAP3K, p38 MAPK, stress response, osmotic stress, heat stress, MAPK signaling, Drosophila, kinase activation
- MeSH terms
- Adaptation, Biological, Amino Acid Sequence, Animals, Drosophila, Environment, Enzyme Activation, Molecular Sequence Data, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases
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