Extracellular signal-regulated kinase-2, but not c-Jun NH2-terminal kinase, activation correlates with surface IgM-mediated apoptosis in the WEHI 231 B cell line.
Both extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) have been implicated in mediating the signaling events that precede apoptosis. We studied the activation of these kinases during apoptosis of WEHI 231 B cells. Surface IgM ligation induces apoptosis of WEHI 231 cells. This effect is augmented by simultaneous engagement of CD95 and is inhibited by costimulation with either CD40 or IL-4R. We determined that surface IgM ligation activates ERK2 to a much greater level than JNK, and that IgM-mediated ERK2 activation is enhanced by costimulation with anti-CD95. Costimulation with either IL-4 or anti-CD40 interferes with anti-IgM-stimulated ERK2 activation. Transient expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) inhibits both ERK2 activation and cell death following stimulation with anti-IgM and the combination of anti-IgM plus anti-CD95. CD40 engagement alone activates JNK, but IL-4 stimulation does not. N-acetyl-L-cysteine pretreatment, which blocks CD40-mediated JNK activation, does not affect the ability of CD40 to inhibit anti-IgM-mediated ERK2 activation and apoptosis. Together, these data suggest that JNK activation is not required for CD40 inhibition of surface IgM-induced cell death and that ERK2 plays an active role in mediating anti-IgM-induced apoptosis of WEHI 231 B cells.
Department of Internal Medicine and Interdisciplinary Program in Immunology, University of Iowa College of Medicine, Iowa City 52242, USA.
J R
JR
Lee
G A
GA
Koretzky
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D019013:CD40 Antigens / Q000276:immunology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018797:Cell Cycle Proteins; D003602:Cytotoxicity, Immunologic; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000276:immunology / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases; D016393:Lymphoma, B-Cell; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; C044203:anti-IgM; D019014:fas Receptor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D017027:Protein Tyrosine Phosphatases; D000111:Acetylcysteine