The MAPKKK Mekk1 regulates the expression of Turandot stress genes in response to septic injury in Drosophila
Open accessAbstract
Septic injury triggers a rapid and widespread response in Drosophila adults that involves the up‐regulation of many genes required to combat infection and for wound healing. Genome‐wide expression profiling has already demonstrated that this response is controlled by signaling through the Toll, Imd, JAK‐STAT and JNK pathways. Using oligonucleotide microarrays, we now demonstrate that the MAPKKK Mekk1 regulates a small subset of genes induced by septic injury including Turandot (Tot) stress genes. Our analysis indicates that Tot genes show a complex regulation pattern including signals from both the JAK‐STAT and Imd pathways and Mekk1. Interestingly, Mekk1 flies are resistant to microbial infection but susceptible to paraquat, an inducer of oxidative stress. These results point to a role of Mekk1 in the protection against tissue damage and/or protein degradation and indicate complex interactions between stress and immune pathways in Drosophila.
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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 [142]
The Introduction identifies Drosophila Mekk1 as a MAPKKK and reports reduced p38 activation in Mekk1 mutants; the Discussion likewise says Mekk1 inhibition reduces p38 activation. Our copy does not specifically state that Mekk1 leads to p38 phosphorylation. The cell-stress clause has separate citations in the citing sentence, so it is not assessed against this source. (LLM, conf=0.84)
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Research works printed but not linked: 5
- De Gregorio, E., Spellman, P.T., Rubin, G.M. & Lemaitre, B. (2001) Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays. Proc. Natl. Acad. Sci. USA 98, 12590-12595.
- Irving, P., Troxler, L., Heuer, T.S., et al. (2001) A genome-wide analysis of immune responses in Drosophila. Proc. Natl. Acad. Sci. USA 98, 15119-15124.
- Lagueux, M., Perrodou, E., Levashina, E.A., Capovilla, M. & Hoffmann, J.A. (2000) Constitutive expression of a com- plement-like protein in toll and JAK gain-of-function mutants of Drosophila. Proc. Natl. Acad. Sci. USA 97, 11427-11432.
- Lemaitre, B., Reichhart, J. & Hoffmann, J. (1997) Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms. Proc. Natl. Acad. Sci. USA 94, 14614-14619.
- Sluss, H.K., Han, Z., Barrett, T., Davis, R.J. & Ip, Y.T. (1996) A JNK signal transduction pathway that mediates morphogenesis Genes to Cells (2006) 11, 397-407 Journal compilation © 2006 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd. 407 and an immune response in Drosophila. Genes Dev. 10, 2745- 2758.
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Ambegaokar, S. S., & Jackson, G. R. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr432 · Cited by 113 · see citing works
Srinivasan, N., Gordon, O., Ahrens, S., Franz, A., Deddouche, S., Chakravarty, P., Phillips, D., Yunus, A. A., Rosen, M. K., Valente, R. S., et al. (2016) · eLife · doi:10.7554/elife.19662 · Cited by 69 · see citing works
- Authors
- Brun, S., Vidal, S., Spellman, P., Takahashi, K., Tricoire, H., & Lemaitre, B.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Howard Hughes Medical Institute (US)
- National Institute of Genetics (JP)
- Institut Jacques Monod (FR)
- Venue
- Genes to Cells
- Publisher
- Wiley
- Published
- 2006-02-28
- Volume
- 11
- Issue
- 4
- Pages
- 397-407
- ISSN
- 1356-9597 (ISSN-L)
- 1365-2443
- OpenAlex
- W2085868830
- Cited by
- 91
- References
- 0
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 2 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 6
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes to Cells (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Schlumberger Foundation
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- MEKK1, MAP3K, septic injury, Drosophila, JAK/STAT signaling, Imd pathway, Toll pathway, oxidative stress, gene expression regulation
- MeSH terms
- Animals, Drosophila, RNA, Messenger, Time Factors, Signal Transduction, Up-Regulation, Oxidative Stress, Sepsis, Insect Proteins, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinase 1, STAT Transcription Factors
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