Mg2+ regulation of kinase signaling and immune function
Year: 2019
Type: article
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.
DOI: 10.1084/jem.20181970
Authors: Chryssa Kanellopoulou, Alex B. George, Evan Masutani, Jennifer L. Cannons, Juan C. Ravell, Tori N. Yamamoto, Margery G. Smelkinson, Ping Du Jiang, Mami Matsuda-Lennikov, Julie Reilley, Robin Handon, Ping-Hsien Lee, J. Richard Miller, Nicholas P. Restifo, Lixin Zheng, Pamela L. Schwartzberg, Matthew Young, Michael J. Lenardo
Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases, University of California San Diego, National Human Genome Research Institute, National Cancer Institute, Center for Cancer Research, University of Pennsylvania, Merck & Co., Inc., Rahway, NJ, USA (United States), University of Michigan, Michigan Medicine
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: hybrid
Funders: U.S. Department of Health and Human Services, Merck, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Allergy and Infectious Diseases, NIH Clinical Center
OpenAlex ID: W2952813280