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CUTTING EDGE |
and p110
Catalytic Isoforms of Phosphatidylinositol 3-Kinase1
* Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge, United Kingdom;
Centre of Biomedicine, Department of Clinical and Biological Sciences, University of Basel, Basel, Switzerland; and
Dipartimento di Biologia Animale e dell’Uomo e Istituto Nazionale per la Fisica della Materia, Universita di Torino, Turin, Italy
The role of PI3K activity in T lymphocyte development is obscure because mice deficient in single PI3K catalytic subunits either die before birth (p110
–/– and p110
–/–) or lack a significant T cell developmental phenotype (p110
–/– and p110
–/–). We have generated mice deficient in both p110 and p110 and show that p110/–/– mice have a profound block in T cell development that occurs at the -selection checkpoint. We show that pre-TCR-induced signaling is significantly reduced in p110/–/– thymocytes and that this results in a concomitant lack of proliferative expansion and increased apoptosis. The survival defect in p110/–/– thymocytes is associated with increased levels of the pro-apoptotic molecule Bcl2 interacting mediator of cell death. This work demonstrates that PI3K activity is critical for T cell development and depends on the combined function of p110 and p110.
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