The Src tyrosine kinase Hck is required for Tel-Abl- but not for Tel-Jak2-induced cell transformation

C. Pecquet (1) , R Nyga , V Penard-Lacronique , T Smithgall , H Murakami , A. Regnier (2) , K Lassoued , F. Gouilleux (3)

1 CHU Tenon [AP-HP]
2 FEMTO-ST - Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174)
3 GICC UMR 6239 CNRS - Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011]

Tel-Abl and Tel-Jak2 are fusion proteins associated with human haematologic neoplasms. They possess constitutive tyrosine kinase activity and activate common downstream signalling pathways like Stat-5, PI3-K/Akt, Ras/MapK and NF-κB. In this study, we showed the specific requirement of Src family members for the Tel-Abl-mediated cell growth, activation of Stat5, PI3-K/Akt and Ras/MapK while dispensable for Tel-Jak2. Hck was found strongly phosphorylated in Tel-Abl-expressing Ba/F3 cells and sensitive to imatinib mesylate treatment, providing evidence that Hck is a target of Tel-Abl tyrosine kinase activity. Overexpression of a kinase dead form of Hck inhibits the proliferation of Ba/F3 cells expressing Tel-Abl as the phosphorylation of Akt and Erk1/2. These results argue for an important role of Hck in Tel-Abl oncogenic signalling.

Domaines: Sciences du Vivant [q-bio]; Cancer

C. Pecquet, R Nyga, V Penard-Lacronique, T Smithgall, H Murakami, et al.. The Src tyrosine kinase Hck is required for Tel-Abl- but not for Tel-Jak2-induced cell transformation. Oncogene, 2007, 26 (11), pp.1577-1585. ⟨10.1038/sj.onc.1209949⟩. ⟨hal-02424613⟩