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The Effects of Cyclosporin A on V(D)J Recombination Activity
Author(s) -
DÖBBELING U.
Publication year - 1997
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1997.d01-426.x
Subject(s) - protein kinase c , calcineurin , recombination , intracellular , microbiology and biotechnology , protein kinase a , chemistry , signal transduction , kinase , biology , biochemistry , medicine , gene , transplantation
V(D)J recombination is up‐regulated by the protein kinase A (PKA) pathway and down‐regulated by the protein kinase C (PKC) and Ca 2+ pathways. When activators of the PKA and PKC pathways or the PKA and Ca 2+ 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 Ca 2+ 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 Ca 2+ 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 Ca 2+ mobilizer CsA increases the V(D)J recombination rate in pre B cells but not in L4 cells.