Abstract
To determine the specificity of signal transducer and activator of transcription (STAT) protein activation by box 3 motif-deficient hematopoietin receptors, expression vectors encoding the receptors for growth hormone, interleukin-3 (IL-3), and IL-4 were transiently transfected into COS-1 cells, together with expression vectors for Janus kinases (JAKs) and STAT proteins. Each receptor mediated a dose-dependent activation of STAT1 and STAT3, and for IL-3R and GHR this process was enhanced by JAK2. The data suggest that a box 3 motif in the cytoplasmic domain of the signal-transducing receptor to the JAK/STAT pathway. Transfection of the receptors, in combination with STAT3, into HepG2 cells reconstituted a cytokine-dependent stimulation of gene transcription through IL-6 response elements, providing evidence for a functional role of STAT3 in controlling gene expression.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Carcinoma, Hepatocellular
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Cell Line
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Chlorocebus aethiops
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Cytokines / pharmacology
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DNA-Binding Proteins / metabolism*
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Enzyme Activation
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Gene Expression / drug effects
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Humans
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Interleukin-6 / pharmacology*
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Janus Kinase 2
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Kinetics
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Liver Neoplasms
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins*
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Receptors, Colony-Stimulating Factor / physiology
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Receptors, Interleukin / drug effects
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Receptors, Interleukin / physiology
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Receptors, Interleukin-3 / biosynthesis
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Receptors, Interleukin-3 / drug effects
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Receptors, Interleukin-3 / physiology*
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Receptors, Interleukin-4
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Receptors, Somatotropin / biosynthesis
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Receptors, Somatotropin / drug effects
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Receptors, Somatotropin / physiology*
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Recombinant Proteins / drug effects
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Recombinant Proteins / metabolism
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STAT3 Transcription Factor
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Signal Transduction
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Trans-Activators / metabolism*
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Transcription, Genetic / drug effects*
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Transfection
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Tumor Cells, Cultured
Substances
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Cytokines
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DNA-Binding Proteins
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Interleukin-6
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Proto-Oncogene Proteins
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Receptors, Colony-Stimulating Factor
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Receptors, Interleukin
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Receptors, Interleukin-3
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Receptors, Interleukin-4
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Receptors, Somatotropin
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Recombinant Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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Trans-Activators
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Protein-Tyrosine Kinases
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JAK2 protein, human
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Janus Kinase 2