This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lierman, E. Articles by Cools, J. PubMed PubMed Citation Articles by Lierman, E. Articles by Cools, J.

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

¹ Department of Molecular and Developmental Genetics, VIB, Leuven
² Center for Human Genetics, KU Leuven, Leuven, Belgium

Correspondence: Jan Cools, VIB11, Campus Gasthuisberg O&N1, Herestraat 49 - box 602, B-3000 Leuven, Belgium. E-mail:jan.cools{at}cme.vib-kuleuven.be

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.

Key words: oncogene, kinase, fusion gene, retroviral insertion screen, signaling, dimerization.