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rdf:type |
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lifeskim:mentions |
umls-concept:C0003320,
umls-concept:C0004561,
umls-concept:C0017262,
umls-concept:C0185117,
umls-concept:C0243044,
umls-concept:C1334474,
umls-concept:C1514873,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1825534,
umls-concept:C2718191,
umls-concept:C2911684
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pubmed:issue |
14
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pubmed:dateCreated |
2002-4-1
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pubmed:abstractText |
A requirement for cyclin D2 in G(1)-to-S phase progression has been definitively established in mature B cells stimulated via the B cell antigen receptor (BCR). However, the identity of constituents of the BCR signaling cascade that leads to cyclin D2 accumulation remains incomplete. We report that inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1/2 blocked BCR-induced activation of extracellular signal-regulated kinase (ERK). Inhibition of the MEK1/2-ERK pathway was sufficient to abrogate BCR-induced cyclin D2 expression at the mRNA and protein levels. Disruption of endogenous heat shock protein 90 (hsp90) function with geldanamycin abrogated BCR-induced cyclin D2 expression and proliferation. Geldanamycin effects were attributed to a selective depletion of cellular Raf-1 that interrupted BCR-coupled activation of MEK1/2 and ERK. By contrast, signaling through the phosphatidylinositol 3-kinase and protein kinase C pathways was not affected, suggesting that disruption of hsp90 function did not cause a general impairment of BCR signaling. These results suggest that the MEK1/2-ERK pathway is essential for BCR signaling to cyclin D2 accumulation in ex vivo splenic B lymphocytes. Furthermore, these findings imply that hsp90 function is required for BCR signaling through the Raf-1-MEK1/2-ERK pathway but not through the phosphatidylinositol 3-kinase- or protein kinase C-dependent pathways.
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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 |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Butadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Ccnd2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/HSP90 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Map2k1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Quinones,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, B-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/U 0126,
http://linkedlifedata.com/resource/pubmed/chemical/geldanamycin
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12144-50
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11823472-Animals,
pubmed-meshheading:11823472-Mice,
pubmed-meshheading:11823472-Spleen,
pubmed-meshheading:11823472-Quinones,
pubmed-meshheading:11823472-Phosphorylation,
pubmed-meshheading:11823472-Benzoquinones,
pubmed-meshheading:11823472-Nitriles,
pubmed-meshheading:11823472-Enzyme Inhibitors,
pubmed-meshheading:11823472-Butadienes,
pubmed-meshheading:11823472-Flavonoids,
pubmed-meshheading:11823472-RNA,
pubmed-meshheading:11823472-Cell Division,
pubmed-meshheading:11823472-Cells, Cultured,
pubmed-meshheading:11823472-Precipitin Tests,
pubmed-meshheading:11823472-RNA, Messenger,
pubmed-meshheading:11823472-Protein Binding,
pubmed-meshheading:11823472-Models, Biological,
pubmed-meshheading:11823472-Enzyme Activation,
pubmed-meshheading:11823472-Mice, Inbred BALB C,
pubmed-meshheading:11823472-B-Lymphocytes,
pubmed-meshheading:11823472-Signal Transduction,
pubmed-meshheading:11823472-Receptors, Antigen, B-Cell,
pubmed-meshheading:11823472-Lactams, Macrocyclic,
pubmed-meshheading:11823472-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11823472-Protein Kinase C,
pubmed-meshheading:11823472-Protein-Tyrosine Kinases,
pubmed-meshheading:11823472-Immunoblotting,
pubmed-meshheading:11823472-Proto-Oncogene Proteins,
pubmed-meshheading:11823472-Cyclins,
pubmed-meshheading:11823472-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11823472-Cyclin-Dependent Kinases,
pubmed-meshheading:11823472-HSP90 Heat-Shock Proteins
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