The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation
Open accessAbstract
Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan parasite that resides inside a parasitophorous vacuole. During infection, Toxoplasma actively remodels the transcriptome of its hosting cells with profound and coupled impact on the host immune response. We report that Toxoplasma secretes GRA24, a novel dense granule protein which traffics from the vacuole to the host cell nucleus. Once released into the host cell, GRA24 has the unique ability to trigger prolonged autophosphorylation and nuclear translocation of the host cell p38α MAP kinase. This noncanonical kinetics of p38α activation correlates with the up-regulation of the transcription factors Egr-1 and c-Fos and the correlated synthesis of key proinflammatory cytokines, including interleukin-12 and the chemokine MCP-1, both known to control early parasite replication in vivo. Remarkably, the GRA24–p38α complex is defined by peculiar structural features and uncovers a new regulatory signaling path distinct from the MAPK signaling cascade and otherwise commonly activated by stress-related stimuli or various intracellular microbes.
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Cites
p38MAPK: stress responses from molecular mechanisms to therapeutics
Coulthard, L. R., White, D. E., Jones, D. L., McDermott, M. F., & Burchill, S. A. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.06.005 · Cited by 691
Alternative p38 activation pathway mediated by T cell receptor-proximal tyrosine kinases
Salvador, J. M., Mittelstadt, P. R., Guszczynski, T., Copeland, T. D., Yamaguchi, H., Appella, E., Fornace, A. J., & Ashwell, J. D. (2005) · Nature Immunology · doi:10.1038/ni1177 · Cited by 306
Chang, C.-I., Xu, B.-E., Akella, R., Cobb, M. H., & Goldsmith, E. J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00525-7 · Cited by 302
Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove
Garai, Á., Zeke, A., Gógl, G., Törő, I., Fördős, F., Blankenburg, H., Bárkai, T., Varga, J., Alexa, A., Emig, D., et al. (2012) · Science Signaling · doi:10.1126/scisignal.2003004 · Cited by 177 · cited 2×
“The GRA24KIM clearly belongs to the tyrosine phosphatase PTPKIM class (defined in Garai et al., 2012; Fig.”
BackgroundDocking Interactions Induce Exposure of Activation Loop in the MAP Kinase ERK2
Zhou, T., Sun, L., Humphreys, J., & Goldsmith, E. J. (2006) · Structure · doi:10.1016/j.str.2006.04.006 · Cited by 164
Structural basis of p38α regulation by hematopoietic tyrosine phosphatase
Francis, D. M., Różycki, B., Koveal, D., Hummer, G., Page, R., & Peti, W. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.707 · Cited by 79
Zhang, Y.-Y., Wu, J.-W., & Wang, Z.-X. (2011) · Science Signaling · doi:10.1126/scisignal.2002241 · Cited by 52 · cited 1×
“7 E) as well as longrange conformational changes, in particular within the activation loop that becomes disor dered, therefore exposing the phosphorylatable Thr180 and Tyr182 residues (Chang et al., 2002; Zhou et al., 2006; Zhang et al., 2011).”
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Cited by
Sangaré, L. O., Yang, N., Konstantinou, E. K., Lu, D., Mukhopadhyay, D., Young, L. H., & Saeij, J. P. J. (2019) · mBio · doi:10.1128/mbio.00808-19 · Cited by 77
Intestinal immune responses to commensal and pathogenic protozoa
Sardinha-Silva, A., Alves-Ferreira, E. V. C., & Grigg, M. E. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.963723 · Cited by 72
Zheng, B., Lou, D., Ding, J., Zhuo, X., Ding, H., Kong, Q., & Lu, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00418 · Cited by 37
Identification of potential molecular mimicry in pathogen-host interactions
(2023) · doi:10.7717/peerj.16339 · Cited by 6
Metadata
- Authors
- Braun, L., Brenier-Pinchart, M.-P., Yogavel, M., Curt-Varesano, A., Curt-Bertini, R.-L., Hussain, T., Kieffer-Jaquinod, S., Coute, Y., Pelloux, H., Tardieux, I., Sharma, A., Belrhali, H., Bougdour, A., & Hakimi, M.-A.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2013-09-16
- Volume
- 210
- Issue
- 10
- Pages
- 2071-2086
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2100868544
- Cited by
- 272
- References
- 7
- FWCI
- 13.27
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Braun, L., Brenier-Pinchart, M.-P., Yogavel, M., Curt-Varesano, A., Curt-Bertini, R.-L., Hussain, T., Kieffer-Jaquinod, S., Coute, Y., Pelloux, H., Tardieux, I., Sharma, A., Belrhali, H., Bougdour, A., & Hakimi, M.-A. (2013). A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20130103
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