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Cited by 214

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Control of the innate immune response by the mevalonate pathway

Open access
Akula, Murali K, Shi, Man, Jiang, Zhaozhao, Foster, Celia E, Miao, David, Li, Annie S, Zhang, Xiaoman, Gavin, Ruth M, Forde, Sorcha D, Germain, Gail, Carpenter, Susan, Rosadini, Charles V, Gritsman, Kira, Chae, Jae Jin, Hampton, Randolph, Silverman, Neal, Gravallese, Ellen M, Kagan, Jonathan C, Fitzgerald, Katherine A, Kastner, Daniel L, Golenbock, Douglas T, Bergo, Martin O, Wang, Donghai·2016·Nature Immunology
DOI 10.1038/ni.3487
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Abstract

Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110δ. Macrophages that were deficient in GGTase I or p110δ exhibited constitutive release of interleukin 1β that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.

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Metadata

Authors
Akula, M. K., Shi, M., Jiang, Z., Foster, C. E., Miao, D., Li, A. S., Zhang, X., Gavin, R. M., Forde, S. D., Germain, G., Carpenter, S., Rosadini, C. V., Gritsman, K., Chae, J. J., Hampton, R., Silverman, N., Gravallese, E. M., Kagan, J. C., Fitzgerald, K. A., Kastner, D. L., Golenbock, D. T., Bergo, M. O., & Wang, D.
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2016-06-06
Volume
17
Issue
8
Pages
922-929
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.3487
OpenAlex
W2418005758
Cited by
214
References
6
FWCI
11.59
Type
journal article
Language
en
Open access
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CoChat. (2026). Citation check: Control of the innate immune response by the mevalonate pathway. https://app.cochat.ai/papers/10.1038/ni.3487
The paper
Akula, M. K., Shi, M., Jiang, Z., Foster, C. E., Miao, D., Li, A. S., Zhang, X., Gavin, R. M., Forde, S. D., Germain, G., Carpenter, S., Rosadini, C. V., Gritsman, K., Chae, J. J., Hampton, R., Silverman, N., Gravallese, E. M., Kagan, J. C., Fitzgerald, K. A., . . . Wang, D. (2016). Control of the innate immune response by the mevalonate pathway. Nature Immunology. https://doi.org/10.1038/ni.3487

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