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PMID: 11139384 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Negative cross-talk between interleukin-3 and interleukin-11 is mediated by suppressor of cytokine signalling-3 (SOCS-3).

The Biochemical journal ·Vol. 353 ·No. Pt 2 ·2001-01-15 ·Pages 223-30

Magrangeas F, Boisteau O, Denis S, Jacques Y, Minvielle S

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.

MeSH Terms
Animals Antigens, CD/metabolism Cell Division/drug effects Cell Line Cytokine Receptor gp130 DNA-Binding Proteins/antagonists & inhibitors,metabolism Interleukin-11/antagonists & inhibitors,pharmacology Interleukin-3/chemistry,pharmacology Membrane Glycoproteins/metabolism Mice Milk Proteins Phosphorylation Proteins/chemistry,genetics,metabolism Receptors, Interleukin/metabolism Repressor Proteins STAT3 Transcription Factor STAT5 Transcription Factor Signal Transduction/drug effects Stem Cells Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins Trans-Activators/antagonists & inhibitors,metabolism Transcription Factors Transfection
Chemicals
Antigens, CD DNA-Binding Proteins Il6st protein, mouse Interleukin-11 Interleukin-3 Membrane Glycoproteins Milk Proteins Proteins Receptors, Interleukin Repressor Proteins STAT3 Transcription Factor STAT5 Transcription Factor Socs3 protein, mouse Stat3 protein, mouse Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins Trans-Activators Transcription Factors Cytokine Receptor gp130
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Magrangeas F
Unité INSERM 463, Institut de Biologie, CHR de Nantes, 9 Quai Moncousu, 44095 Nantes Cedex 01, France.
Boisteau O
Denis S
Jacques Y
Minvielle S
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/0264-6021:3530223
Published
2001-01-15
Pages
223-30
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1221562
Subset
IM
External Links
PubMed source DOI: 10.1042/0264-6021:3530223 PMC Full Text View journal details
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