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

PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia / Felli, MARIA PIA; Vacca, Alessandra; Calce, A; Bellavia, Diana; Campese, Antonio Francesco; Grillo, R; DI GIOVINE, M; Checquolo, Saula; Talora, Claudio; Palermo, Rocco; DI MARIO, G; Frati, Luigi; Gulino, Alberto; Screpanti, Isabella. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 24(6):(2005), pp. 992-1000. [10.1038/sj.onc.1208302]

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

FELLI, MARIA PIA;VACCA, Alessandra;BELLAVIA, Diana;CAMPESE, Antonio Francesco;CHECQUOLO, Saula;TALORA, Claudio;PALERMO, ROCCO;FRATI, Luigi;GULINO, Alberto;SCREPANTI, Isabella
2005

Abstract

Protein kinase (PK)Ctheta is a critical regulator of mature T-cell activation and proliferation, being implicated in TCR-triggered nuclear factor (NF)-kB activation and providing important survival signals to leukemic T cells. We previously showed that overexpression of pTalpha/pre- TCR and constitutive activation of NF-kB characterize the T-cell leukemia/lymphoma developing in Notch3-IC transgenic mice. We report here that PKCtheta is a downstream target of Notch3 signaling and that its activation and membrane translocation require a functional pre-TCR in order to trigger NF-kB activation in thymocytes and lymphoma cells of transgenic mice. Furthermore, deletion of PKCtheta in Notch3-IC transgenic mice reduces the incidence of leukemia, correlating with decreased NF-kB activation. This paper therefore suggests that PKCtheta mediates the activation of NF-kB by pre-TCR in immature thymocytes and contributes to the development of Notch3-dependent T-cell lymphoma.
2005
01 Pubblicazione su rivista::01a Articolo in rivista
PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia / Felli, MARIA PIA; Vacca, Alessandra; Calce, A; Bellavia, Diana; Campese, Antonio Francesco; Grillo, R; DI GIOVINE, M; Checquolo, Saula; Talora, Claudio; Palermo, Rocco; DI MARIO, G; Frati, Luigi; Gulino, Alberto; Screpanti, Isabella. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 24(6):(2005), pp. 992-1000. [10.1038/sj.onc.1208302]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/358248
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