[HTML][HTML] Identification of protein tyrosine kinases with oncogenic potential using a retroviral insertion mutagenesis screen

E Lierman, H Van Miegroet, E Beullens, J Cools - haematologica, 2009 - ncbi.nlm.nih.gov
E Lierman, H Van Miegroet, E Beullens, J Cools
haematologica, 2009ncbi.nlm.nih.gov
Protein tyrosine kinases form a large family of signaling proteins implicated in both normal
and malignant cell signaling. The aim of this study was to identify protein tyro-sine kinases
that can transform hematopoietic cells to growth factor independent proliferation when
constitutively activated by homodimerization. We used a modified retroviral insertion
mutagenesis screen with a retroviral vector containing the homodimerization domain of
ETV6 followed by an artificial splice donor site. Integration of this retroviral vector within a …
Abstract
Protein tyrosine kinases form a large family of signaling proteins implicated in both normal and malignant cell signaling. The aim of this study was to identify protein tyro-sine kinases that can transform hematopoietic cells to growth factor independent proliferation when constitutively activated by homodimerization. We used a modified retroviral insertion mutagenesis screen with a retroviral vector containing the homodimerization domain of ETV6 followed by an artificial splice donor site. Integration of this retroviral vector within a gene of the host genome would generate a fusion transcript containing the dimerization domain and part of the disrupted gene. Using this strategy with the IL3 dependent Ba/F3 cell line, we identified 8 different protein tyrosine kinases (Abl1, Fgfr1, Hck, Jak2, Lck, Mertk, Mst1r, Tnk1) that transformed the cells. These results characterize HCK, MERTK, MST1R and TNK1 as potential oncogenes and describe a method to identify gain-of-function fusion genes using a retroviral insertion screen.
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