Abstract
Previous studies have shown that addition of interleukin-3 (IL-3) abrogated the B-cell potential of primary colonies supported by IL-11, erythropoietin, IL-7 and steel factor. However, the mechanism by which IL-3 exerts its inhibitory role is not understood. Using a variant of the mouse pro-B cell line Ba/F3 which expresses both IL-3 and IL-11 receptors, we showed that pretreatment of these cells with IL-3 before stimulation by IL-11 suppressed the tyrosine phosphorylation and nuclear translocation of STAT3 (signal transducer and activator of transcription 3). This inhibition occurred within 30 min and required the synthesis of a negative regulator. The onset of IL-3-dependent inhibition was correlated temporally with the appearance of SOCS-3 (suppressor of cytokine signalling-3) protein. In addition, overexpression of SOCS-3 in the pro-B cell line effectively blocked STAT3 activation induced by IL-11. These findings establish that a cytokine (IL-3) that has been shown to modulate its own signal of activation is also able to down-regulate signalling activated by a different cytokine (IL-11). This cross-talk involves activation of the JAK (Janus kinase)/STAT signalling pathway, but not mitogen-activated protein kinase pathways, and is mediated, at least in part, by SOCS-3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / metabolism
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Cell Division / drug effects
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Cell Line
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Cytokine Receptor gp130
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism
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Interleukin-11 / antagonists & inhibitors
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Interleukin-11 / pharmacology*
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Interleukin-3 / chemistry
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Interleukin-3 / pharmacology*
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Membrane Glycoproteins / metabolism
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Mice
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Milk Proteins*
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Phosphorylation
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Proteins / chemistry*
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Proteins / genetics
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Proteins / metabolism
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Receptors, Interleukin / metabolism
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Repressor Proteins*
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STAT3 Transcription Factor
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STAT5 Transcription Factor
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Signal Transduction / drug effects
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Stem Cells
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / metabolism
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Transcription Factors*
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Transfection
Substances
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Antigens, CD
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DNA-Binding Proteins
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Il6st protein, mouse
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Interleukin-11
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Interleukin-3
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Membrane Glycoproteins
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Milk Proteins
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Proteins
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Receptors, Interleukin
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Repressor Proteins
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STAT3 Transcription Factor
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STAT5 Transcription Factor
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Socs3 protein, mouse
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Stat3 protein, mouse
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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Trans-Activators
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Transcription Factors
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Cytokine Receptor gp130