Abstract
Signal Transducer and Activator of Transcription (STATs) are important mediators of cytokine and growth factor-induced signal transduction. STAT5A and STAT5B have been shown to play a role in survival and proliferation of hematopoietic cells both in vitro and in vivo and to contribute to the growth and viability of cells transformed by the TEL-JAK2 oncoprotein. In this study, we investigated the molecular mechanisms by which constitutively active STAT5 proteins induce cell proliferation and survival of Ba/F3 cell lines expressing either dominant positive STAT5A or STAT5B variants or TEL-JAK2 or TEL-ABL fusion proteins. Our results showed that active STAT5 constitutively interacted with p85, the regulatory subunit of the PI 3-kinase. A constitutive activity of the PI 3-kinase/Akt pathway was observed in these cells and required for their cell cycle progression. In contrast, while activity of the PI 3-kinase/Akt pathway was required for survival of Ba/F3 cells expressing the constitutively active forms of STAT5A or STAT5B, it was dispensable for cells transformed by TEL-JAK2 or TEL-ABL fusion proteins, suggesting that additional survival pathways take place in these transformed cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Cycle / physiology
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Cell Division / physiology
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Cell Line
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Cell Survival / physiology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Enzyme Activation
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Erythropoietin / pharmacology
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Fusion Proteins, bcr-abl / biosynthesis
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Fusion Proteins, bcr-abl / physiology
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / enzymology
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Humans
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Mice
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Milk Proteins*
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Oncogene Proteins, Fusion / biosynthesis
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Oncogene Proteins, Fusion / physiology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphatidylinositol 3-Kinases / physiology*
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-akt
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STAT5 Transcription Factor
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Signal Transduction / physiology*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Trans-Activators / physiology*
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Transformation, Genetic
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Tumor Suppressor Proteins
Substances
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DNA-Binding Proteins
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Milk Proteins
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Oncogene Proteins, Fusion
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Proto-Oncogene Proteins
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STAT5 Transcription Factor
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STAT5A protein, human
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STAT5B protein, human
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Stat5a protein, mouse
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Stat5b protein, mouse
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TEL-ABL fusion protein, human
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TEL-JAK2 fusion protein, human
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TEL-JAK2 fusion protein, mouse
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Trans-Activators
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Tumor Suppressor Proteins
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Erythropoietin
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Protein-Tyrosine Kinases
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Fusion Proteins, bcr-abl
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt