PKC?mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia.

Protein kinase (PK)C?is a critical regulator of mature T-cell activation and proliferation, being implicated in TCR-triggered nuclear factor (NF)-?B activation and providing important survival signals to leukemic T cells. We previously showed that overexpression of pTa/pre-TCR and constitutive activation of NF-?B characterize the T-cell leukemia/lymphoma developing in Notch3-IC transgenic mice. We report here that PKC?is a downstream target of Notch3 signaling and that its activation and membrane translocation require a functional pre-TCR in order to trigger NF-?B activation in thymocytes and lymphoma cells of transgenic mice. Furthermore, deletion of PKC?in Notch3-IC transgenic mice reduces the incidence of leukemia, correlating with decreased NF-?B activation. This paper therefore suggests that PKC?mediates the activation of NF-?B by pre-TCR in immature thymocytes and contributes to the development of Notch3-dependent T-cell lymphoma.Oncogene (2005) 24, 992-1000. doi:10.1038/sj.onc.1208302 Published online 13 December 2004 [ABSTRACT FROM AUTHOR]