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PMID: 12591901 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production.

The Journal of experimental medicine ·Vol. 197 ·No. 4 ·2003-02-17 ·Pages 425-36

Matsumoto A, Seki Y, Watanabe R, Hayashi K, Johnston JA, Harada Y, Abe R, Yoshimura A, Kubo M

Abstract

Suppressor of cytokine signaling (SOCS)3 has been characterized as a negative feedback regulator in cytokine-mediated Janus kinase signal transducer and activator of transcription signaling. However, this study shows that T cells from transgenic mice expressing SOCS3 exhibit a significant reduction in interleukin (IL)-2 production induced by T cell receptor cross-linking when T cells are costimulated with CD28. Decreased protein expression in SOCS3(+/-) mice enhanced CD28-mediated IL-2 production, clearly indicating the correlation between expression level of SOCS3 and IL-2 production ability. The SOCS3 protein interacted with phosphorylated CD28 through its SH2 domain but not the kinase inhibitory region. In addition, a point mutation in the SOCS3 SH2 domain attenuated the inhibition of CD28 function in IL-2 promoter activation. Committed T helper (Th)2 cells exclusively expressed SOCS3 and production of Th2 cytokines, such as IL-4 and IL-5, was much less dependent on CD28 costimulation compared with interferon gamma and IL-2 production in Th1 cells. Consistent with this notion, the expression level of SOCS3 in early T cell activation influenced the ability of IL-2 production induced by CD28 costimulation. Therefore, the SOCS3 may play an alternative role in prohibiting excessive progression of CD28-mediated IL-2 production.

MeSH Terms
Animals CD28 Antigens/physiology Humans Interleukin-2/biosynthesis,genetics Interleukin-4/pharmacology Jurkat Cells Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Transgenic Phosphatidylinositol 3-Kinases/physiology Phosphorylation Promoter Regions, Genetic Proteins/physiology Receptors, Antigen, T-Cell/physiology Repressor Proteins Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins T-Lymphocytes/immunology Transcription Factors Tyrosine/metabolism src Homology Domains
Chemicals
CD28 Antigens Interleukin-2 Proteins Receptors, Antigen, T-Cell Repressor Proteins SOCS3 protein, human Socs3 protein, mouse Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins Transcription Factors Interleukin-4 Tyrosine Phosphatidylinositol 3-Kinases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Matsumoto Akira
Research Institute for Biological Sciences, Tokyo University of Science, Chiba 278-0022, Japan.
Seki Yoh-ichi
Watanabe Ryosuke
Hayashi Katsuhiko
Johnston James A
Harada Yohsuke
Abe Ryo
Yoshimura Akihiko
Kubo Masato
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42 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20020939
Published
2003-02-17
Pages
425-36
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193868
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20020939 PMC Full Text View journal details
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