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CTLA‐4 interacts with STAT5 and inhibits STAT5‐mediated transcription
Author(s) -
Srahna M.,
Grunsven L. A.,
Remacle J. E.,
Vandenberghe P.
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02313.x
Subject(s) - cd28 , cytotoxic t cell , jurkat cells , ctla 4 , t cell , stat5 , cd86 , microbiology and biotechnology , biology , cd80 , il 2 receptor , signal transduction , cd40 , immune system , immunology , biochemistry , in vitro
Summary Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4; CD152) is a member of the immunoglobulin gene superfamily with strong homology to the receptor CD28 with which it shares the ligands CD80 and CD86. Unlike CD28, a potent costimulator of T‐cell responses, CTLA‐4 is transiently expressed on the cell surface of activated T cells and appears to operate predominantly as a negative regulator of T‐cell proliferation. Signal transduction mechanisms utilized by CTLA‐4 remain unclear although several mechanisms have been implicated. In this study, we show that the cytoplasmic domain of CTLA‐4, but not of CD28, binds to STAT5 in yeast two‐hybrid assay and in coimmunoprecipitation assays. Mutations of Tyr165 and Tyr182 in CTLA‐4 did not abrogate the interaction of STAT5 with CTLA‐4. Finally, the overexpression of CTLA‐4 in Jurkat T cells inhibits STAT‐mediated activation of STAT5 responsive elements. These results suggest that CTLA‐4 and STAT5 interact in T cells and that this interaction is important for CTLA‐4 signalling.