TEL/PDGFβR fusion protein activates STAT1 and STAT5: A common mechanism for transformation by tyrosine kinase fusion proteins

13. TEL/PDGFβR fusion protein activates STAT1 and STAT5: A common mechanism for transformation by tyrosine kinase fusion proteins Pages 584-593 Alyson M. Wilbanks, Sudipta Mahajan, David A. Frank, Brian J. Druker, D.Gary Gilliland, Martin Carroll Preview Purchase PDF (797 K) | Related Articles Abstract | Figures/Tables | References Abstract Objective TEL/PDGFβR is a tyrosine kinase fusion protein associated with the pathogenesis of chronic myelomonocytic leukemia. The following experiments were undertaken to understand the mechanisms whereby TEL/PDGFβR transforms cells. Materials and Methods Activation of JAK and STAT proteins was studied in an interleukin 3 (IL-3)-dependent cell line, Ba/F3, transformed to IL-3 independence by TEL/PDGFβR. Results TEL/PDGFβR activates STAT1 and STAT5 in transformed Ba/F3 cells through a JAK-independent pathway. Activation of STAT proteins requires the kinase activity of TEL/PDGFβR. JAK1, JAK2, JAK3, and TYK2 are not phosphorylated by TEL/PDGFβR. However, TEL/PDGFβR can phosphorylate STAT5 in transiently transfected COS cells, suggesting that TEL/PDGFβR may itself be the kinase involved in tyrosine phosphorylation of STAT proteins. In contrast, native PDGFβR stimulated by PDGF ligand does not activate STAT proteins to a significant degree in this hematopoietic context. STAT1 and STAT5 also are activated by TEL/ABL and TEL/JAK2 fusion proteins associated with human leukemia. Conclusions STAT activation may be a common mechanism of transformation by leukemogenic tyrosine kinase fusion proteins.