Constitutive pre-TCR signaling promotes differentiation through Ca²⁺ mobilization and activation of NF-κB 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-κB and NFAT in developing T cells.