Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-kappa B 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-T CR 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 cyt osolic Ca2+ concentration. In addition, we show that constitutive pre-TCR s ignaling is associated with an increased rate of Ca2+ influx through store- operated plasma membrane Ca2+ channels,We show also that the biphasic natur e of the observed pre-TCR-induced rise in cytosolic Ca2+ differentially mod ulates the activities of the transcription factors NF-kappaB and NFAT in de veloping T cells.