Dual-Specificity Phosphatases in Immunity and Infection: An Update
| Autor: | Faizal A. M. Raffi, Roland Lang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular T cell Inflammation Review macrophage Biology Infections MAPK phosphatase Catalysis Gene Expression Regulation Enzymologic lcsh:Chemistry Inorganic Chemistry Immune system Antigen Immunity medicine Animals Humans ddc:610 Physical and Theoretical Chemistry atypical DUSP lcsh:QH301-705.5 Molecular Biology Spectroscopy Innate immune system Kinase Organic Chemistry General Medicine cytokines Computer Science Applications Cell biology medicine.anatomical_structure lcsh:Biology (General) lcsh:QD1-999 Dual-Specificity Phosphatases Mitogen-Activated Protein Kinase Phosphatases medicine.symptom Mitogen-Activated Protein Kinases |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 20, Iss 11, p 2710 (2019) |
| ISSN: | 1422-0067 |
| Popis: | Kinase activation and phosphorylation cascades are key to initiate immune cell activation in response to recognition of antigen and sensing of microbial danger. However, for balanced and controlled immune responses, the intensity and duration of phospho-signaling has to be regulated. The dual-specificity phosphatase (DUSP) gene family has many members that are differentially expressed in resting and activated immune cells. Here, we review the progress made in the field of DUSP gene function in regulation of the immune system during the last decade. Studies in knockout mice have confirmed the essential functions of several DUSP-MAPK phosphatases (DUSP-MKP) in controlling inflammatory and anti-microbial immune responses and support the concept that individual DUSP-MKP shape and determine the outcome of innate immune responses due to context-dependent expression and selective inhibition of different mitogen-activated protein kinases (MAPK). In addition to the canonical DUSP-MKP, several small-size atypical DUSP proteins regulate immune cells and are therefore also reviewed here. Unexpected and complex findings in DUSP knockout mice pose new questions regarding cell type-specific and redundant functions. Another emerging question concerns the interaction of DUSP-MKP with non-MAPK binding partners and substrate proteins. Finally, the pharmacological targeting of DUSPs is desirable to modulate immune and inflammatory responses. |
| Databáze: | OpenAIRE |
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