title: A G protein-associated ERK pathway is involved in LPS-induced proliferation and a PTK-associated p38 MAPK pathway is involved in LPS-induced differentiation in resting B cells.
abstract: We, previously, showed that PKC-dependent ERK/p38 MAPK activation was inhibited by treating the resting B cell line 38B9 with an anti-MHC class II antibody. Further studies in this work demonstrated that PKA was involved in lipopolysaccharide (LPS)-induced proliferation of the cells, such that the PKC inhibitor activated PKA with concomitant LPS-induced proliferation but not IgG secretion. Consequently, the PKA inhibitor down-regulated ERK and p38 MAPK, and decreased cell proliferation. In addition, the treatment of LPS-stimulated 38B9 cells with PTK inhibitor reduced PKC- and PKA-dependent p38 MAPK activation and reduced the level of IgG secretion rather than the level of proliferation. However, the treatment of LPS-stimulated 38B9 cells with pertussis toxin (PTX), an inhibitor for the G protein-coupled receptor, inhibited the activation of both PKC- and PKA-dependent ERK and significantly reduced LPS-induced proliferation but not IgG secretion. Furthermore, ERK and p38 MAPK inhibitors reduced LPS-induced proliferation and differentiation, respectively, in 38B9 cells in a dose-dependent manner. These results suggest that LPS-induced proliferation of resting B cells is mainly mediated through a G protein-associated PKA/PKC-dependent ERK pathway and that a PTK-associated PKC/PKA-dependent p38 MAPK pathway is mostly involved in LPS-induced differentiation of the resting B cells.
authors.affiliation: Division of Biological Sciences and the Institute for Molecular Biology and Genetics, Chonbuk National University, Chonju 561-756, Republic of Korea.
authors.forename: Ju
authors.initials: J
authors.lastname: Kim
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Yang
authors.forename: Yong-Suk
authors.initials: YS
authors.lastname: Jang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020962:Heterotrimeric GTP-Binding Proteins