Signaling by the Kinase MINK Is Essential in the Negative Selection of Autoreactive Thymocytes

Nat Immunol. 2005 Jan;6(1):65-72. doi: 10.1038/ni1145. Epub 2004 Dec 19.

Abstract

Signaling through the T cell antigen receptor leading to elimination (negative selection) or differentiation (positive selection) of developing thymocytes generates a self-tolerant T cell repertoire. Here we report that the serine-threonine kinase MINK selectively connects the T cell receptor to a signaling pathway that mediates negative but not positive selection. Analysis of this pathway suggested that the essential function of MINK in the elimination of self-reactive thymocytes may be associated with 'downstream' activation of Jun kinase and enhancement of expression of the proapoptotic molecule Bim.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Down-Regulation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / physiology*
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / enzymology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology*
  • Thymus Gland / enzymology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism

Substances

  • Kcne1 protein, mouse
  • Potassium Channels, Voltage-Gated
  • Receptors, Antigen, T-Cell