Mg2+ regulation of kinase signaling and immune function.
J Exp Med
; 216(8): 1828-1842, 2019 08 05.
Article
em En
| MEDLINE
| ID: mdl-31196981
ABSTRACT
Mg2+ is required at micromolar concentrations as a cofactor for ATP, enzymatic reactions, and other biological processes. We show that decreased extracellular Mg2+ reduced intracellular Mg2+ levels and impaired the Ca2+ flux, activation marker up-regulation, and proliferation after T cell receptor (TCR) stimulation. Reduced Mg2+ specifically impairs TCR signal transduction by IL-2-inducible T cell kinase (ITK) due to a requirement for a regulatory Mg2+ in the catalytic pocket of ITK. We also show that altered catalytic efficiency by millimolar changes in free basal Mg2+ is an unrecognized but conserved feature of other serine/threonine and tyrosine kinases, suggesting a Mg2+ regulatory paradigm of kinase function. Finally, a reduced serum Mg2+ concentration in mice causes an impaired CD8+ T cell response to influenza A virus infection, reduces T cell activation, and exacerbates morbidity. Thus, Mg2+ directly regulates the active site of specific kinases during T cell responses, and maintaining a high serum Mg2+ concentration is important for antiviral immunity in otherwise healthy animals.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
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Linfócitos T CD4-Positivos
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Infecções por Orthomyxoviridae
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Linfócitos T CD8-Positivos
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Vírus da Influenza A Subtipo H1N1
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Magnésio
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article