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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1999-4-13
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pubmed:abstractText |
Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) is a cell surface receptor expressed on activated T cells that can inhibit T cell responses induced by activation of the TCR and CD28. Studies with phosphorylated peptides based on the CTLA-4 intracellular domain have suggested that tyrosine phosphorylation of CTLA-4 may regulate its interactions with cytoplasmic proteins that could determine its intracellular trafficking and/or signal transduction. However, the kinase(s) that phosphorylate CTLA-4 remain uncharacterized. In this report, we show that CTLA-4 can associate with the Src kinases Fyn and Lck and that transfection of Fyn or Lck, but not the unrelated kinase ZAP70, can induce tyrosine phosphorylation of CTLA-4 on residues Y201 and Y218. A similar pattern of tyrosine phosphorylation was found in pervanadate-treated Jurkat T cells stably expressing CTLA-4. Phosphorylation of CTLA-4 Y201 in Jurkat cells correlated with cell surface accumulation of CTLA-4. CTLA-4 phosphorylation induced the association of CTLA-4 with the tyrosine phosphatase SHP-2, but not with phosphatidylinositol 3-kinase. In contrast, Lck-induced phosphorylation of CD28 resulted in the recruitment of phosphatidylinositol 3-kinase, but not SHP-2. These findings suggest that phosphorylation of CD28 and CTLA-4 by Lck activates distinct intracellular signaling pathways. The association of CTLA-4 with Src kinases and with SHP-2 results in the formation of a CTLA-4 complex with the potential to regulate T cell activation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/FYN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Specific Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fyn,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
162
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1270-7
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:9973379-Amino Acid Sequence,
pubmed-meshheading:9973379-Antigens, CD,
pubmed-meshheading:9973379-Antigens, Differentiation,
pubmed-meshheading:9973379-Binding Sites,
pubmed-meshheading:9973379-CTLA-4 Antigen,
pubmed-meshheading:9973379-Cell Line,
pubmed-meshheading:9973379-Cell Membrane,
pubmed-meshheading:9973379-Humans,
pubmed-meshheading:9973379-Immunoconjugates,
pubmed-meshheading:9973379-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:9973379-Jurkat Cells,
pubmed-meshheading:9973379-Lymphocyte Activation,
pubmed-meshheading:9973379-Lymphocyte Specific Protein Tyrosine Kinase p56(lck),
pubmed-meshheading:9973379-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:9973379-Phosphorylation,
pubmed-meshheading:9973379-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:9973379-Protein Tyrosine Phosphatase, Non-Receptor Type 6,
pubmed-meshheading:9973379-Protein Tyrosine Phosphatases,
pubmed-meshheading:9973379-Proto-Oncogene Proteins,
pubmed-meshheading:9973379-Proto-Oncogene Proteins c-fyn,
pubmed-meshheading:9973379-Signal Transduction,
pubmed-meshheading:9973379-T-Lymphocytes,
pubmed-meshheading:9973379-Transfection,
pubmed-meshheading:9973379-Tyrosine,
pubmed-meshheading:9973379-src-Family Kinases
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pubmed:year |
1999
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pubmed:articleTitle |
Regulation of cytotoxic T lymphocyte-associated molecule-4 by Src kinases.
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pubmed:affiliation |
Gwen Knapp Center for Lupus and Immunology Research, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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