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.
Original language | English |
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Pages (from-to) | 1577-1585 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 26 |
Issue number | 11 |
DOIs | |
Publication status | Published - 8 Mar 2007 |
Externally published | Yes |
Keywords
- Hck
- Oncogenes
- Signal transduction
- Src kinases
- Tel-Abl
- Tel-Jak2