Src family kinases interfere with dimerization of STAT5A through a phosphotyrosine-SH2 domain interaction.

ABSTRACT:

Background

Chronic myeloid leukemia (CML) is driven by the expression of the BCR-ABL oncoprotein. STAT5 is a BCR-ABL substrate and persistently activated by tyrosine phosphorylation in CML cells. Activated STAT5 (pSTAT5) drives proliferation and survival of leukemic cells and contributes to initial transformation and maintenance of the disease. In cytokine-induced STAT5 signaling, phosphorylation of STAT5A on Y694 leads to nuclear accumulation of the transcription factor, followed by DNA-binding and gene induction. However, Src-family kinases (SFK) mediate cytoplasmic retention of pSTAT5A leading to attenuated target gene expression and colony formation in CML cells.

Results

In this study we show that autophosphorylation of Y416 in the highly conserved activation loop of SFK

SUBMITTER: Fahrenkamp D 

PROVIDER: S-EPMC4350284 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature