PKCθ mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia

Maria Pia Felli, Alessandra Vacca, Angelica Calce, Diana Bellavia, Antonio F. Campese, Rita Grillo, Monica Di Giovine, Saula Checquolo, Claudio Talora, Rocco Palermo, Giuseppina Di Mario, Luigi Frati, Alberto Gulino, Isabella Screpanti

Research output: Contribution to journalArticlepeer-review

Abstract

Protein kinase (PK)Cθ is a critical regulator of mature T-cell activation and proliferation, being implicated in TCR-triggered nuclear factor (NF)-κB activation and providing important survival signals to leukemic T cells. We previously showed that overexpression of pTα/pre-TCR and constitutive activation of NF-κB characterize the T-cell leukemia/lymphoma developing in Notch3-IC transgenic mice. We report here that PKCθ is a downstream target of Notch3 signaling and that its activation and membrane translocation require a functional pre-TCR in order to trigger NF-κB activation in thymocytes and lymphoma cells of transgenic mice. Furthermore, deletion of PKCθ in Notch3-IC transgenic mice reduces the incidence of leukemia, correlating with decreased NF-κB activation. This paper therefore suggests that PKCθ mediates the activation of NF-κB by pre-TCR in immature thymocytes and contributes to the development of Notch3-dependent T-cell lymphoma.

Original languageEnglish
Pages (from-to)992-1000
Number of pages9
JournalOncogene
Volume24
Issue number6
DOIs
Publication statusPublished - Feb 3 2005

Keywords

  • Leukemia
  • NF-κB
  • Notch3
  • PKCθ
  • T cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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