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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2003-2-13
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pubmed:abstractText |
Infection of bovine T cells and B cells with the intracellular protozoan parasite Theileria parva induces a transformed phenotype with characteristics comparable to leukemic cells. The transformed phenotype reverts on drug-induced parasite death, and the cured lymphocytes acquire a resting phenotype and eventually die by apoptosis if not further stimulated. Here, we show that both lymphocyte proliferation and activation of the transcription factor AP-1 are mediated by Src-family protein tyrosine kinases (PTKs) in a parasite-dependent fashion. Src-family PTKs are known to be present in glycolipid-enriched microdomains (GEMs), also called lipid rafts, and to be negatively regulated by PTK Csk complexed to tyrosine-phosphorylated transmembrane adapter protein PAG (phosphoprotein associated with GEMs) also called Cbp (Csk-binding protein). We, therefore, purified GEMs from proliferating infected B cells and from growth-arrested cells that had been drug-cured of parasites. Proliferation arrest led to a striking increase of PAG/Cbp expression; correspondingly, the amount of Csk associated with PAG/Cbp in GEMs increased markedly, whereas PTK Hck accumulation in GEM fractions did not alter on growth arrest. We propose that Theileria-induced lymphocyte proliferation and permanent activation of Hck stems from down-regulation of PAG/Cbp and the concomitant constitutive loss of the negative regulator Csk from the GEMs of transformed B cells.
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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/AG 1879,
http://linkedlifedata.com/resource/pubmed/chemical/Antiprotozoal Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CSK tyrosine-protein kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-hck,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/buparvaquone,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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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 |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1874-81
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:12411311-Animals,
pubmed-meshheading:12411311-Antiprotozoal Agents,
pubmed-meshheading:12411311-B-Lymphocytes,
pubmed-meshheading:12411311-Cattle,
pubmed-meshheading:12411311-Cell Division,
pubmed-meshheading:12411311-Cell Transformation, Neoplastic,
pubmed-meshheading:12411311-Enzyme Activation,
pubmed-meshheading:12411311-Enzyme Inhibitors,
pubmed-meshheading:12411311-Lymphocyte Activation,
pubmed-meshheading:12411311-Membrane Microdomains,
pubmed-meshheading:12411311-Membrane Proteins,
pubmed-meshheading:12411311-Naphthoquinones,
pubmed-meshheading:12411311-Phenotype,
pubmed-meshheading:12411311-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12411311-Phosphoproteins,
pubmed-meshheading:12411311-Protein-Tyrosine Kinases,
pubmed-meshheading:12411311-Proto-Oncogene Proteins,
pubmed-meshheading:12411311-Proto-Oncogene Proteins c-hck,
pubmed-meshheading:12411311-Pyrimidines,
pubmed-meshheading:12411311-Signal Transduction,
pubmed-meshheading:12411311-Theileria parva,
pubmed-meshheading:12411311-Transcription Factor AP-1,
pubmed-meshheading:12411311-src-Family Kinases
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pubmed:year |
2003
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pubmed:articleTitle |
Constitutive exclusion of Csk from Hck-positive membrane microdomains permits Src kinase-dependent proliferation of Theileria-transformed B lymphocytes.
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pubmed:affiliation |
Laboratoire de Signalisation Immunoparasitaire, Département d'Immunologie, Institut Pasteur, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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