TEL/PDGFbetaR fusion protein activates STAT1 and STAT5: a common mechanism for transformation by tyrosine kinase fusion proteins - PubMed (original) (raw)

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

A M Wilbanks et al. Exp Hematol. 2000 May.

Free article

Abstract

Objective: TEL/PDGFbetaR 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/PDGFbetaR 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/PDGFbetaR.

Results: TEL/PDGFbetaR activates STAT1 and STAT5 in transformed Ba/F3 cells through a JAK-independent pathway. Activation of STAT proteins requires the kinase activity of TEL/PDGFbetaR. JAK1, JAK2, JAK3, and TYK2 are not phosphorylated by TEL/PDGFbetaR. However, TEL/PDGFbetaR can phosphorylate STAT5 in transiently transfected COS cells, suggesting that TEL/PDGFbetaR may itself be the kinase involved in tyrosine phosphorylation of STAT proteins. In contrast, native PDGFbetaR 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.

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TEL/PDGFbetaR fusion protein activates STAT1 and STAT5: a common mechanism for transformation by tyrosine kinase fusion proteins - PubMed (original) (raw)