Mg²⁺ regulation of kinase signaling and immune function.

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 kinas

SUBMITTER: Kanellopoulou C 

PROVIDER: S-EPMC6683994 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature