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  • Title: PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia.
    Author: Felli MP, Vacca A, Calce A, Bellavia D, Campese AF, Grillo R, Di Giovine M, Checquolo S, Talora C, Palermo R, Di Mario G, Frati L, Gulino A, Screpanti I.
    Journal: Oncogene; 2005 Feb 03; 24(6):992-1000. PubMed ID: 15592506.
    Abstract:
    Protein kinase (PK)C theta is a critical regulator of mature T-cell activation and proliferation, being implicated in TCR-triggered nuclear factor (NF)-kappa B activation and providing important survival signals to leukemic T cells. We previously showed that overexpression of pT alpha/pre-TCR and constitutive activation of NF-kappa B characterize the T-cell leukemia/lymphoma developing in Notch3-IC transgenic mice. We report here that PKC theta is a downstream target of Notch3 signaling and that its activation and membrane translocation require a functional pre-TCR in order to trigger NF-kappa B activation in thymocytes and lymphoma cells of transgenic mice. Furthermore, deletion of PKC theta in Notch3-IC transgenic mice reduces the incidence of leukemia, correlating with decreased NF-kappa B activation. This paper therefore suggests that PKC theta mediates the activation of NF-kappa B by pre-TCR in immature thymocytes and contributes to the development of Notch3-dependent T-cell lymphoma.
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