DUSP meet immunology: dual specificity MAPK phosphatases in control of the inflammatory response.
The MAPK family members p38, JNK, and ERK are all activated downstream of innate immunity's TLR to induce the production of cytokines and inflammatory mediators. However, the relative intensity and duration of the activation of different MAPK appears to determine the type of immune response. The mammalian genome encodes a large number of dual specificity phosphatases (DUSP), many of which act as MAPK phosphatases. In this study, we review the emergence of several DUSP as genes that are differentially expressed and regulated in immune cells. Recently, a series of investigations in mice deficient in DUSP1, DUSP2, or DUSP10 revealed specificity in the regulation of the different MAPK proteins, and defined essential roles in models of local and systemic inflammation. The DUSP family is proposed as a set of molecular control devices specifying and modulating MAPK signaling, which may be targeted to unleash or attenuate innate and adaptive immune effector functions.
Lang
Roland
R
Institute of Medical Microbiology, Immunology and Hygiene, Technical University Munich, Immunology and Hygiene, Trogerstrasse 30, Munich 81675, Germany. Roland.Lang@lrz.tum.de
Hammer
Michael
M
Mages
Jörg
J
D000818:Animals; D054638:Dual Specificity Phosphatase 1; D015870:Gene Expression / Q000276:immunology*; D006801:Humans; D007249:Inflammation; D008262:Macrophage Activation / Q000276:immunology*; D051379:Mice; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases