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

Tijdschriftbijdrage - Tijdschriftartikel

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.
Tijdschrift: HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
ISSN: 0390-6078
Issue: 10
Volume: 94
Pagina's: 1440 - 1444
Jaar van publicatie:2009
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:6
CSS-citation score:1
Authors from:Government, Higher Education