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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1997-6-26
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pubmed:abstractText |
Signals transduced through CD40 rescue cells of the Ramos-Burkitt lymphoma (Ramos-BL) B cell line from surface immunoglobulin M (sIgM)-triggered growth arrest and apoptosis. This study investigates whether protein tyrosine kinase (PTK) activity and tyrosine phosphorylation on p95(vav) and on the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3 kinase) play a role in the regulation of Ramos-BL B cell survival. The PTK inhibitor herbimycin A (HA) triggers significant growth arrest prior to apoptosis from the G1-phase of the cell cycle, indicating that tyrosine phosphorylation of key proteins is critical for Ramos-BL cell cycle progression and survival. Indeed, signals transduced through CD40 fail to rescue Ramos-BL B cells from HA-triggered growth arrest and apoptosis. Since Vav and PI3 kinase are intimately involved in the regulation of cellular growth, their tyrosine phosphorylation status was determined in unstimulated and anti-IgM- and anti-CD40-treated Ramos-BL B cells: Vav and p85 are devoid of tyrosine-phosphorylated epitopes in control cells whereas p85, but not Vav, is significantly phosphorylated following ligation of sIgM and anti-CD40 triggers tyrosine phosphorylation on both proteins. Thus, tyrosine-phosphorylated Vav may be a critical effector of CD40-mediated survival. As tyrosine-phosphorylated PI3 kinase is common to both sIgM-triggered death and CD40-triggered survival pathways, its lipid kinase activity was correlated with tyrosine phosphorylation on p85: Ramos-BL B cells exhibit high basal levels of PI3 kinase activity, determined by immunoprecipitation with anti-p85 and 32P incorporation into phosphatidylinositol, which is not significantly affected by stimulation with anti-IgM but which is elevated by 36 +/- 2.9% following ligation of CD40. Thus, tyrosine phosphorylation on p85 correlates with the CD40-triggered increase in PI3 kinase activity but not with basal levels nor with sIgM-triggered levels of enzymatic activity: these data suggest the presence of different PI3 kinase isoforms or the existence of multiple regulatory pathways for the same PI3 kinase isotype in Ramos-BL B cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin M,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-vav,
http://linkedlifedata.com/resource/pubmed/chemical/Quinones,
http://linkedlifedata.com/resource/pubmed/chemical/VAV1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/herbimycin,
http://linkedlifedata.com/resource/pubmed/chemical/secretory IgM
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0008-8749
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
177
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
119-28
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9178638-Antigens, CD40,
pubmed-meshheading:9178638-B-Lymphocytes,
pubmed-meshheading:9178638-Benzoquinones,
pubmed-meshheading:9178638-Burkitt Lymphoma,
pubmed-meshheading:9178638-Cell Cycle Proteins,
pubmed-meshheading:9178638-Child, Preschool,
pubmed-meshheading:9178638-Enzyme Inhibitors,
pubmed-meshheading:9178638-G1 Phase,
pubmed-meshheading:9178638-Humans,
pubmed-meshheading:9178638-Immunoglobulin M,
pubmed-meshheading:9178638-Lactams, Macrocyclic,
pubmed-meshheading:9178638-Male,
pubmed-meshheading:9178638-Neoplasm Proteins,
pubmed-meshheading:9178638-Palatine Tonsil,
pubmed-meshheading:9178638-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:9178638-Phosphorylation,
pubmed-meshheading:9178638-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:9178638-Protein Processing, Post-Translational,
pubmed-meshheading:9178638-Proto-Oncogene Proteins,
pubmed-meshheading:9178638-Proto-Oncogene Proteins c-vav,
pubmed-meshheading:9178638-Quinones,
pubmed-meshheading:9178638-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
CD40-triggered protein tyrosine phosphorylation on Vav and on phosphatidylinositol 3-kinase correlates with survival of the Ramos-Burkitt lymphoma B cell line.
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pubmed:affiliation |
Department of Biochemistry, University of Oxford, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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