Differential activation and regulation of mitogen-activated protein kinases through the antigen receptor and CD40 in human B cells.
In human B cells, antigen receptor ligation and CD40 ligation are known to activate the extracellular-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK) pathways, which in turn regulate many important B cell functions. We previously reported that antigen receptor ligation activated the ERK pathway whereas CD40 ligation activated the JNK/stress-activated protein kinase (SAPK) pathway. Here, we demonstrate that another SAPK, p38/Hog1, is activated by both antigen receptor ligation or CD40 ligation in a human B-lymphoblastoid cell line and tonsillar B cells. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, partially inhibited ERK2 and p38 activation triggered through the B cell receptor whereas activation of JNK1 and p38 through CD40 was not affected. PD98059, a specific inhibitor of mitogen-activated extracellular response kinase kinase (MEK), significantly inhibited ERK2 activation and partially inhibited p38 activation triggered by anti-IgM antibody treatment, but did not affect CD40-dependent signaling events. In addition, anti-IgM antibody-induced signaling pathways were shown to be PKC-dependent in contrast to the CD40-induced signaling pathways. Thus, the B cell receptor and CD40 recruit the ERK, JNK and p38 pathways by using different upstream effectors.
Sakata
N
N
Division of Basic Sciences, Department of Pediatrics and the Program in Molecular Signal Transduction, National Jewish Medical and Research Center, Denver, USA.
Kawasome
H
H
Terada
N
N
Gerwins
P
P
Johnson
G L
GL
Gelfand
E W
EW
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008024:Ligands; D020930:MAP Kinase Kinase Kinases / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D011493:Protein Kinase C / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens; D007075:Immunoglobulin M; D008024:Ligands; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D023201:CD40 Ligand; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases