Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-kappaB and NFAT

Nat Immunol. 2001 May;2(5):403-9. doi: 10.1038/87704.


Pre-T cell antigen receptor (pre-TCR) signaling plays a crucial role in the development of immature T cells. Although certain aspects of proximal pre-TCR signaling have been studied, the intermediate signal transducers and the distal transcription modulators have been poorly characterized. We report here a correlation between pre-TCR signaling and a biphasic rise in the cytosolic Ca2+ concentration. In addition, we show that constitutive pre-TCR signaling is associated with an increased rate of Ca2+ influx through store-operated plasma membrane Ca2+ channels. We show also that the biphasic nature of the observed pre-TCR-induced rise in cytosolic Ca2+ differentially modulates the activities of the transcription factors NF-kappaB and NFAT in developing T cells.

Publication types

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

MeSH terms

  • Animals
  • Calcium Signaling*
  • Cell Differentiation
  • DNA-Binding Proteins / metabolism*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology*
  • Immediate-Early Proteins / metabolism
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Mutant Strains
  • Models, Genetic
  • Monomeric GTP-Binding Proteins / metabolism
  • NF-kappa B / metabolism*
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Receptors, Antigen, T-Cell, alpha-beta
  • Selection, Genetic
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Immediate-Early Proteins
  • Membrane Glycoproteins
  • NF-kappa B
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Transcription Factors
  • V(D)J recombination activating protein 2
  • pre-T cell receptor alpha
  • GEM protein, human
  • Gem protein, mouse
  • Monomeric GTP-Binding Proteins