title: Rac/ROS-related protein kinase C and phosphatidylinositol-3-kinase signaling are involved in a negative regulating cascade in B cell activation by antibody-mediated cross-linking of MHC class II molecules.
abstract: In addition to their essential role in antigen presentation, MHC class II molecules have been widely described as receptors associated with signal transduction involved in regulating B cell function. However, their precise function and mechanism in signal transduction are not yet fully elucidated. Our previous studies demonstrated that cross-linking of MHC class II molecules led to the inhibition of resting B cell activation in which various signal molecules were involved. Especially, Rac-associated ROS-dependent MAP kinases, including ERK1/2 and p38, are involved in MHC class II-associated negative signal transduction in the phorbol 12, 13-dibutyrate (PDBU)-treated, but not LPS-treated, resting B cell line, 38B9. In this study, we further illustrated that PKC regulates downstream signal molecules, including MAP kinases and NF-kappaB in PDBU-stimulated resting B cells, together with Rac and ROS. In addition, we found that phosphatidylinositol 3-kinase (PI3K)-dependent activation of ERK/p38 MAP kinases was associated with the signaling procedure in PDBU-induced B cell activation. Collectively, Rac/ROS-related PKC and PI3K signaling are involved in a negative regulation cascade through the cross-linking of MHC class II molecules by anti-MHC class II antibodies in resting B cells.
authors: Division of Biological Sciences and the Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors: Hee-Young
authors: HY
authors: Yang
authors: Ju
authors: J
authors: Kim
authors: Kyung-Yeol
authors: KY
authors: Lee
authors: Yong-Suk
authors: YS
authors: Jang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007211:Indoles / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000906:Antibodies; D000949:Histocompatibility Antigens Class II; D007211:Indoles; D008301:Maleimides; D015240:Phorbol 12,13-Dibutyrate; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D017382:Reactive Oxygen Species; D020744:rac GTP-Binding Proteins; C088060:bisindolylmaleimide