Regulation of T cell development and activation by creatine kinase B

PLoS One. 2009;4(4):e5000. doi: 10.1371/journal.pone.0005000. Epub 2009 Apr 1.

Abstract

Creatine kinase catalyzes the reversible transfer of the N-phosphoryl group from phosphocreatine to ADP to generate ATP and plays a key role in highly energy-demanding processes such as muscle contraction and flagellar motility; however, its role in signal transduction (which frequently involves ATP-consuming phosphorylation) and consequent cell-fate decisions remains largely unknown. Here we report that creatine kinase B was significantly up-regulated during the differentiation of double-positive thymocytes into single-positive thymocytes. Ectopic expression of creatine kinase B led to increased ATP level and enhanced phosphorylation of the TCR signaling proteins. Consequentially, transgenic expression of creatine kinase B promoted the expression of Nur77 and Bim proteins and the cell death of TCR signaled thymocyte. In addition, the activation, proliferation and cytokine secretion of T cells were also enhanced by the expression of creatine kinase B transgene. In contrast, treatment of T cells with specific creatine kinase inhibitor or creatine kinase B shRNA resulted in severely impaired T cell activation. Taken together, our results indicate that creatine kinase B plays an unexpected role in modulating TCR-mediated signaling and critically regulates thymocyte selection and T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage
  • Creatine Kinase / metabolism
  • Creatine Kinase / physiology*
  • Lymphocyte Activation / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phosphorylation
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • Thymus Gland / cytology
  • Up-Regulation

Substances

  • Creatine Kinase