Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-kappaB and NFAT.
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.
Aifantis
I
I
Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Gounari
F
F
Scorrano
L
L
Borowski
C
C
von Boehmer
H
H
D000818:Animals; D020013:Calcium Signaling; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D017874:Immediate-Early Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008957:Models, Genetic; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012641:Selection, Genetic; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; C090377:pre-T cell receptor alpha; C490245:GEM protein, human; C088119:Gem protein, mouse; D020559:Monomeric GTP-Binding Proteins