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

Citation
Am. Wilbanks et al., TEL/PDGF beta R fusion protein activates STAT1 and STAT5: A common mechanism for transformation by tyrosine kinase fusion proteins, EXP HEMATOL, 28(5), 2000, pp. 584-593
Citations number
53
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
EXPERIMENTAL HEMATOLOGY
ISSN journal
0301472X → ACNP
Volume
28
Issue
5
Year of publication
2000
Pages
584 - 593
Database
ISI
SICI code
0301-472X(200005)28:5<584:TBRFPA>2.0.ZU;2-X
Abstract
Objective. TEL/PDGF beta R is a tyrosine kinase fusion protein associated w ith the pathogenesis of chronic myelomonocytic leukemia, The following expe riments were undertaken to understand the mechanisms whereby TEL/PDGF beta R transforms cells. Materials and Methods. Activation of JAK: and STAT proteins was studied in an interleukin 3 (IL3)-dependent cell line, Ba/F3, transformed to IL-3 inde pendence by TEL/PDGF beta R. Results. TEL/PDGF beta R activates STAT1 and STAT5 in transformed Ba/F3 cel ls through a JAK-independent pathway. Activation of STAT proteins requires the kinase activity of TEL/PDGF beta R, JAK1, JAK2, JAK3, and TYK2 are not phosphorylated by TEL/PDGR beta R. However, TEL/PDGF beta R can phosphoryla te STAT5 in transiently transfected COS tells, suggesting that TEL/PDGF bet a R may itself be the kinase involved in tyrosine phosphorylation of STAT p roteins. In contrast, native PDGF beta R stimulated by PDGF ligand does not activate STAT proteins to a significant degree in this hematopoietic conte xt. STAT1 and STAT5 also are activated by TEL/ABL and TEL/JAK2. fusion prot eins associated with human leukemia, Conclusions. STAT activation may be a common mechanism of transformation by leukemogenic tyrosine kinase fusion proteins. (C) 2000 International Socie ty for Experimental Hematology. Published by Elsevier Science Inc.