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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0031727,
umls-concept:C0037083,
umls-concept:C0109317,
umls-concept:C0185117,
umls-concept:C0252527,
umls-concept:C0752312,
umls-concept:C0851285,
umls-concept:C1120843,
umls-concept:C1150579,
umls-concept:C1155065,
umls-concept:C1314939,
umls-concept:C1333340,
umls-concept:C1334474,
umls-concept:C1366876,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1710082,
umls-concept:C2911684
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pubmed:issue |
1-2
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pubmed:dateCreated |
2005-1-24
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pubmed:abstractText |
Recent evidence has implicated galectins and their carbohydrate ligands as novel regulators of T-cell homeostasis. Galectin-1 (Gal-1), a member of this family, inhibits clonal expansion, induces apoptosis of antigen-primed T lymphocytes and suppresses the development of T-cell-mediated autoimmune diseases in vivo. Because the beta-galactoside-binding protein is expressed in activated but not resting T cells, it has been hypothesized that Gal-1-induced apoptosis may constitute an autocrine suicide mechanism to eliminate activated T cells contributing to the termination of an effector immune response. We undertook this study to investigate the signals and intracellular pathways leading to Gal-1 expression during T-cell activation. When T cells were stimulated either with anti-CD3 or anti-CD28 monoclonal antibody plus PMA in the presence of accessory cells, a sustained up-regulation of Gal-1 was observed, reaching a plateau between days 3 and 5 following CD3 engagement or costimulation through CD28. Investigation of the signal transduction events involved in this process revealed a role for Lck and Fyn kinases, since the Src kinase inhibitor PP1 inhibited the up-regulated expression of Gal-1 following T-cell activation. Downstream signaling routes involve mitogen-activated protein kinase (MAPK) kinase (MEK)1/extracellular signal-regulated kinase (ERK) and p38 MAPK, as Gal-1 expression was prevented by U0126 and SB202190. In addition, expression of Gal-1 involves interleukin (IL)-2-dependent signaling routes triggered by p70S6 kinase, as it could be inhibited by rapamycin. This is the first demonstration of the intracellular pathways that control activation-induced expression of Gal-1, which may reveal potential targets for immune intervention to modulate expression of this beta-galactoside-binding protein in pathological disorders.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-(4-fluorophenyl)-2-(4-hydroxypheny...,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Butadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/FYN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Galectin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Specific Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
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/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, 70-kDa,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/U 0126,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0300-8177
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
267
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
177-85
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15663199-Antibodies, Monoclonal,
pubmed-meshheading:15663199-Blotting, Western,
pubmed-meshheading:15663199-Butadienes,
pubmed-meshheading:15663199-Cell Proliferation,
pubmed-meshheading:15663199-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:15663199-Enzyme Inhibitors,
pubmed-meshheading:15663199-Galectin 1,
pubmed-meshheading:15663199-Gene Expression Regulation,
pubmed-meshheading:15663199-Humans,
pubmed-meshheading:15663199-Imidazoles,
pubmed-meshheading:15663199-Interleukin-2,
pubmed-meshheading:15663199-Leukocytes, Mononuclear,
pubmed-meshheading:15663199-Lymphocyte Activation,
pubmed-meshheading:15663199-Lymphocyte Specific Protein Tyrosine Kinase p56(lck),
pubmed-meshheading:15663199-MAP Kinase Kinase 1,
pubmed-meshheading:15663199-Models, Biological,
pubmed-meshheading:15663199-Nitriles,
pubmed-meshheading:15663199-Proto-Oncogene Proteins,
pubmed-meshheading:15663199-Proto-Oncogene Proteins c-fyn,
pubmed-meshheading:15663199-Pyridines,
pubmed-meshheading:15663199-Ribosomal Protein S6 Kinases, 70-kDa,
pubmed-meshheading:15663199-Signal Transduction,
pubmed-meshheading:15663199-Sirolimus,
pubmed-meshheading:15663199-T-Lymphocytes,
pubmed-meshheading:15663199-Tetradecanoylphorbol Acetate,
pubmed-meshheading:15663199-Time Factors,
pubmed-meshheading:15663199-Up-Regulation,
pubmed-meshheading:15663199-p38 Mitogen-Activated Protein Kinases,
pubmed-meshheading:15663199-src-Family Kinases
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pubmed:year |
2004
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pubmed:articleTitle |
Regulated expression of galectin-1 during T-cell activation involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase and p70S6 kinase.
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pubmed:affiliation |
Division of Immunogenetics, Hospital de Clínicas José de San Martín, Department of Microbiology, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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