Involvement of stress-activated protein kinase and p38 mitogen-activated protein kinase in mIgM-induced apoptosis of human B lymphocytes.
Despite intensive efforts, the intracellular signaling pathways that mediate apoptosis remain unclear. The human B lymphoma cell line, B104, possesses characteristics that make it an attractive model for analysis of receptor-mediated apoptosis. Although these cells express both membrane IgM (mIgM) and membrane IgD (mIgD) crosslinking mIgM results in significant apoptosis while crosslinking mIgD does not. Our results show that crosslinking mIgM but not mIgD induced a delayed and sustained activation of the mitogen-activated protein kinase (MAPK) family members stress-activated protein kinase (SAPK) and p38 MAPK. The calcium ionophore ionomycin, which also induces apoptosis in B104 cells, stimulated a similar SAPK and p38 MAPK response. Cyclosporin A, a potent inhibitor of apoptosis induced by either mIgM or ionomycin, inhibited activation of both SAPK and p38 MAPK, suggesting that stimulation of these kinases may be required for induction of apoptosis. Collectively, our results indicate that SAPK and p38 MAPK may be downstream targets during mIgM-induced, calcium-mediated, apoptosis in human B lymphocytes.
Graves
J D
JD
Department of Pharmacology, University of Washington Medical Center, Seattle 98195, USA.
Draves
K E
KE
Craxton
A
A
Saklatvala
J
J
Krebs
E G
EG
Clark
E A
EA
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000502:physiology; D003432:Cross-Linking Reagents; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007072:Immunoglobulin D / Q000502:physiology; D007075:Immunoglobulin M / Q000276:immunology / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D016393:Lymphoma, B-Cell; D020928:Mitogen-Activated Protein Kinases; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D003432:Cross-Linking Reagents; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D015759:Ionomycin; D016572:Cyclosporine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases