Abstract
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.
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Acknowledgements
This work was supported by grants from ARC (Association de la Recherche contre le Cancer), Ligue contre le Cancer (Comité du Nord-Pas de Calais), Conseil Régional de Picardie, Fondation de France, Cent pour Sang la Vie and National Institutes of Health (grant CA101828 to TES). CP is supported by ARERS-Verre Espoir and Fondation pour la Recherche Médicale and R N by the ‘Ministere de la Recherche’.
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Pecquet, C., Nyga, R., Penard-Lacronique, V. et al. The Src tyrosine kinase Hck is required for Tel-Abl- but not for Tel-Jak2-induced cell transformation. Oncogene 26, 1577–1585 (2007). https://doi.org/10.1038/sj.onc.1209949
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DOI: https://doi.org/10.1038/sj.onc.1209949
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