Linked Life Data

11937539

Source:http://linkedlifedata.com/resource/pubmed/id/11937539

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-4-8
pubmed:abstractText
One of the major unresolved questions in B cell biology is how the B cell Ag receptor (BCR) differentially signals to transduce anergy, apoptosis, proliferation, or differentiation during B cell maturation. We now report that extracellularly regulated kinase-mitogen-activated protein kinase (Erk-MAP kinase) can play dual roles in the regulation of the cell fate of the immature B cell lymphoma, WEHI-231, depending on the kinetics and context of Erk-MAP kinase activation. First, we show that the BCR couples to an early (< or =2 h) Erk-MAP kinase signal which activates a phospholipase A(2) pathway that we have previously shown to mediate collapse of mitochondrial membrane potential, resulting in depletion of cellular ATP and cathepsin B execution of apoptosis. Rescue of BCR-driven apoptosis by CD40 signaling desensitizes such early extracellularly regulated kinase (Erk) signaling and hence uncouples the BCR from the apoptotic mitochondrial phospholipase A(2) pathway. A second role for Erk-MAP kinase in promoting the growth and proliferation of WEHI-231 immature B cells is evidenced by data showing that proliferating and CD40-stimulated WEHI-231 B cells exhibit a sustained cycling pattern (8-48 h) of Erk activation that correlates with cell growth and proliferation. This growth-promoting role for Erk signaling is supported by three key pieces of evidence: 1) signaling via the BCR, under conditions that induce growth arrest, completely abrogates sustained Erk activation; 2) CD40-mediated rescue from growth arrest correlates with restoration of cycling Erk activation; and 3) sustained inhibition of Erk prevents CD40-mediated rescue of BCR-driven growth arrest of WEHI-231 immature B cells. Erk-MAP kinase can therefore induce diverse biological responses in WEHI-231 cells depending on the context and kinetics of activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3855-64
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11937539-Animals, pubmed-meshheading:11937539-Antibodies, Anti-Idiotypic, pubmed-meshheading:11937539-Antigens, CD40, pubmed-meshheading:11937539-Apoptosis, pubmed-meshheading:11937539-B-Lymphocyte Subsets, pubmed-meshheading:11937539-Butadienes, pubmed-meshheading:11937539-Cell Cycle, pubmed-meshheading:11937539-Cell Death, pubmed-meshheading:11937539-Cell Differentiation, pubmed-meshheading:11937539-Cell Survival, pubmed-meshheading:11937539-Down-Regulation, pubmed-meshheading:11937539-Enzyme Activation, pubmed-meshheading:11937539-Enzyme Inhibitors, pubmed-meshheading:11937539-Flavonoids, pubmed-meshheading:11937539-Growth Inhibitors, pubmed-meshheading:11937539-Lymphoma, B-Cell, pubmed-meshheading:11937539-MAP Kinase Signaling System, pubmed-meshheading:11937539-Mice, pubmed-meshheading:11937539-Mitogen-Activated Protein Kinases, pubmed-meshheading:11937539-Nitriles, pubmed-meshheading:11937539-Receptors, Antigen, B-Cell, pubmed-meshheading:11937539-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Differential roles for extracellularly regulated kinase-mitogen-activated protein kinase in B cell antigen receptor-induced apoptosis and CD40-mediated rescue of WEHI-231 immature B cells.
pubmed:affiliation
Department of Immunology and Bacteriology, University of Glasgow, Glasgow, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't