Abstract
GM-CSF signals through JAK2 and STAT5 and stimulates the expression of STAT5 target genes, such as pim-1 and CIS. Analyzed by EMSA, GM-CSF stimulation led to much stronger STAT5 DNA-binding to pim-1 or CIS GAS elements in primary human monocytes compared with mature macrophages. Similarly, GM-CSF-induced expression of pim-1 and CIS mRNAs was much stronger in monocytes. These differencies were not a result of downregulation of the GM-CSF receptor system or STAT5 expression, because monocytes and macrophages readily expressed GM-CSF receptor, JAK2, STAT5A, and STAT5B mRNAs and proteins. Monocytes expressed significant amounts of truncated STAT5 forms that took part in STAT5-DNA complex formation in GM-CSF-stimulated monocytes. This resulted in faster moving STAT5 complexes compared with macrophages in EMSA. Our results demonstrate that STAT5 isoform expression, GM-CSF-induced STAT5 activation, and STAT5 target-gene expression are altered significantly during monocyte/macrophage differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cells, Cultured
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DNA-Binding Proteins / physiology*
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
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Humans
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Immediate-Early Proteins / genetics
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Macrophages / cytology
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Macrophages / physiology*
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Milk Proteins*
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Monocytes / cytology
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Monocytes / physiology*
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Protein Serine-Threonine Kinases / genetics
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-pim-1
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STAT5 Transcription Factor
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Suppressor of Cytokine Signaling Proteins
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Trans-Activators / physiology*
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Tumor Suppressor Proteins
Substances
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DNA-Binding Proteins
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Immediate-Early Proteins
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Milk Proteins
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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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Suppressor of Cytokine Signaling Proteins
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Trans-Activators
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Tumor Suppressor Proteins
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cytokine inducible SH2-containing protein
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Granulocyte-Macrophage Colony-Stimulating Factor
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PIM1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-pim-1