Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Sci. Signal., 14 October 2008
Vol. 1, Issue 41, p. pe44
[DOI: 10.1126/scisignal.141pe44]
PERSPECTIVES
Acetylation of MKP-1 and the Control of Inflammation
Hongbo Chi1* and
Richard A. Flavell2,3*
1 Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA. 2 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA. 3 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Abstract:
Innate immune responses mediated by Toll-like receptors (TLRs), a class of pattern-recognition receptors, play a critical role in the defense against microbial pathogens. However, excessive TLR-mediated responses result in sepsis, autoimmunity, and chronic inflammation. To prevent deleterious activation of TLRs, cells have evolved multiple mechanisms that inhibit innate immune reactions. Stimulation of TLRs induces the expression of the gene encoding the mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a nuclear-localized dual-specificity phosphatase that preferentially dephosphorylates p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in the attenuation of TLR-triggered production of proinflammatory cytokines. MKP-1 is posttranslationally modified by multiple mechanisms, including phosphorylation. A study now demonstrates that MKP-1 is also acetylated on a key lysine residue following stimulation of TLRs. Acetylation of MKP-1 promotes the interaction of MKP-1 with its substrate p38 MAPK, which results in dephosphorylation of p38 MAPK and the inhibition of innate immunity.
Steroid-Insensitive ERK1/2 Activity Drives CXCL8 Synthesis and Neutrophilia by Airway Smooth Muscle.
S. Robins, L. Roussel, A. Schachter, P.-A. Risse, A. K. Mogas, R. Olivenstein, J. G. Martin, Q. Hamid, and S. Rousseau (2011)
Am. J. Respir. Cell Mol. Biol.
45, 984-990
|Abstract »|Full Text »|PDF »
Receptor for Advanced Glycation End-Products Signals through Ras during Tobacco Smoke-Induced Pulmonary Inflammation.
P. R. Reynolds, S. D. Kasteler, R. E. Schmitt, and J. R. Hoidal (2011)
Am. J. Respir. Cell Mol. Biol.
45, 411-418
|Abstract »|Full Text »|PDF »
MAPK Phosphatase-1 (MKP-1) Expression Is Up-Regulated by hCG/cAMP and Modulates Steroidogenesis in MA-10 Leydig Cells.
L. Brion, P. M. Maloberti, N. V. Gomez, C. Poderoso, A. B. Gorostizaga, M. M. Mori Sequeiros Garcia, A. B. Acquier, M. Cooke, C. F. Mendez, E. J. Podesta, et al. (2011)
Endocrinology
152, 2665-2677
|Abstract »|Full Text »|PDF »
Inhibition of MAPK by Prolactin Signaling through the Short Form of Its Receptor in the Ovary and Decidua: INVOLVEMENT OF A NOVEL PHOSPHATASE.
Y. S. Devi, A. M. Seibold, A. Shehu, E. Maizels, J. Halperin, J. Le, N. Binart, L. Bao, and G. Gibori (2011)
J. Biol. Chem.
286, 7609-7618
|Abstract »|Full Text »|PDF »
Dysregulation of p38 and MKP-1 in Response to NOD1/TLR4 Stimulation in Sarcoid Bronchoalveolar Cells.
R. Rastogi, W. Du, D. Ju, G. Pirockinaite, Y. Liu, G. Nunez, and L. Samavati (2011)
Am. J. Respir. Crit. Care Med.
183, 500-510
|Abstract »|Full Text »|PDF »
Suppressing LPS-induced early signal transduction in macrophages by a polyphenol degradation product: a critical role of MKP-1.
Z. Tucsek, B. Radnai, B. Racz, B. Debreceni, J. K. Priber, T. Dolowschiak, T. Palkovics, F. Gallyas Jr, B. Sumegi, and B. Veres (2011)
J. Leukoc. Biol.
89, 105-111
|Abstract »|Full Text »|PDF »
The dual-specificity MAP kinase phosphatases: critical roles in development and cancer.
O. Bermudez, G. Pages, and C. Gimond (2010)
Am J Physiol Cell Physiol
299, C189-C202
|Abstract »|Full Text »|PDF »
Editorial: Leishmania survival mechanisms: the role of host phosphatases.
M. T. Shio and M. Olivier (2010)
J. Leukoc. Biol.
88, 1-3
|Full Text »|PDF »
