u-0126 has been researched along with Lymphoma--B-Cell* in 1 studies
1 other study(ies) available for u-0126 and Lymphoma--B-Cell
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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.
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. Topics: Animals; Antibodies, Anti-Idiotypic; Apoptosis; B-Lymphocyte Subsets; Butadienes; CD40 Antigens; Cell Cycle; Cell Death; Cell Differentiation; Cell Survival; Down-Regulation; Enzyme Activation; Enzyme Inhibitors; Flavonoids; Growth Inhibitors; Lymphoma, B-Cell; MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinases; Nitriles; Receptors, Antigen, B-Cell; Tumor Cells, Cultured | 2002 |