GLOBAL DISCOVERY OF DYSREGULATED PROTEIN EXPRESSION AND PHOSPHORYLATION NETWORKS IDENTIFIED LEO1 AS A KEY TARGET OF PRL-3 PHOSPHATASE IN LEUKEMOGENESIS

Abstract

PRL-3, an oncogenic dual-specificity phosphatase, is over-expressed in 50% of AML and associated with poor survival. We found that stable expression of PRL-3 in the cytokine-dependent TF-1 AML cells confers cytokine-independent growth, induces colony-forming ability in methylcellulose media and tumorigenesis in vivo. However, how PRL-3 mediates these functions in AML is unknown. To systematically characterize novel substrates of PRL-3 in leukemia, unbiased large-scale proteomics and phosphoproteomics analyses were performed between the parental TF-1 cells and their malignant PRL-3 transfectant counterparts to discover critical differences in signaling networks.