Live free or die: an immature T cell decision encoded in distinct Bcl-2 sensitive and insensitive Ca2+ signals.
In the developing thymus, strong T cell receptor (TCR) activation by self-antigens induces negative selection and weak TCR activation induces positive selection. Both processes are mediated by Ca(2+) signals, raising the question of how a single second messenger like Ca(2+) can mediate such diverse cell fates. Recent findings indicate that graded TCR activation signals are encoded in distinct patterns of Ca(2+) elevation. The anti-apoptotic protein Bcl-2 discriminates between these Ca(2+) signaling patterns, selectively inhibiting pro-apoptotic Ca(2+) signals induced by strong TCR activation without suppressing pro-survival Ca(2+) signals induced by weak TCR activation.
Davis
Michael C
MC
Department of Medicine, Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
Distelhorst
Clark W
CW
D017209:Apoptosis; D020013:Calcium Signaling; D002470:Cell Survival; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology
D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell