1. ¹Department of Experimental Medicine and Pathology, University 'La Sapienza', 00161 Roma, Italy
2. ²Department of Experimental Medicine, University of L'Aquila, 67100 L'Aquila, Italy
3. ³Neuromed Institute, 86077 Pozzilli, Italy
4. ⁴Istituto Pasteur-Fondazione Cenci Bolognetti, University 'La Sapienza', 00161 Roma, Italy

Correspondence: I Screpanti, Laboratory of Molecular Pathology, Dipartimento di Medicina Sperimentale e Patologia, University 'La Sapienza', Viale Regina Elena 324, 00161 Roma, Italy. E-mail: isabella.screpanti@uniroma1.it

⁵These authors contributed equally to this work

Received 6 August 2004; Revised 15 October 2004; Accepted 18 October 2004; Published online 13 December 2004.

Abstract

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 pT/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.