The effects of cyclosporin A on V(D)J recombination activity.
V(D)J recombination is up-regulated by the protein kinase A (PKA) pathway and down-regulated by the protein kinase C (PKC) and Ca2+ pathways. When activators of the PKA and PKC pathways or the PKA and Ca2+ pathways are given at the same time, a strong reduction of the PKA effect is observed. The V(D)J recombination suppressing effect of elevated intracellular Ca2+ levels, but not that of the PKC pathway, can be abrogated by the addition of the calcineurin inhibitor cyclosporin A (CsA), indicating that the effect of Ca2+ is mediated by calcineurin. This effect is observed in a pre B cell line as well as in the V(D)J recombination competent fibroblast cell line L4, indicating that the mechanisms of the cross talk between different signalling pathways are basically the same in both cell types. In the absence of Ca2+ mobilizer CsA increases the V(D)J recombination rate in pre B cells but not in L4 cells.
Döbbeling
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Dermatology Department, University Hospital of Zürich, Switzerland.
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019703:Calcineurin; D002118:Calcium / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors*; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D004789:Enzyme Activation; D015322:Gene Rearrangement, B-Lymphocyte / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000378:metabolism; D011995:Recombination, Genetic / Q000187:drug effects*
D002148:Calmodulin-Binding Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D016572:Cyclosporine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D002118:Calcium