| Rapid immunosuppressive effects of glucocorticoids mediated through Lck and Fyn (2005) | |||||||||
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Abstract | |||||||||
| IMMUNOBIOLOGY Rapid immunosuppressive effects glucocorticoids mediated through Lck and Fyn Mark Lowenberg Jurriaan Tuynman Joyce Bilderbeek Timo Gaber Frank Buttgereit Sander van Deventer Maikel Peppelenbosch and Daniel Hommes Glucocorticoids GCs are effective immunosuppressive agents and mediate wellde ned transcriptional effects via receptors There increasing evidence that GCs also initiate rapid nongenomic signaling events Using activated human lymphocytes and peptide array containing different kinase consensus substrates generated comprehensive pro induced rapid effects signal transduction The results show marked early differences phosphorylation between pretreated cells and control cells including impaired phosphorylation lck fyn Lck Fyn consensus substrates Immunoprecipita tion and vitro kinase assays reveal rapid induced down modulation Lck and Fyn kinases using SAM Src src associated mitosis kDa substrate Additionally immunoprecipitation experiments revealed reduced Lck and Fyn associations suggesting inhibited recruitment these kinases the cell receptor complex Western blot analysis revealed reduced phosphorylation series downstream signaling intermediates following treatment including protein kinase PKB protein kinase PKC and mitogen activated protein kinases MAPKs Experiments with receptor negative Jurkat cells and pharmacologic receptor ligand indicated that rapid inhibition Lck and Fyn kinases receptor dependent Parallel experiments conducted following the applic | |||||||||
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Cited publications (3) | |||||||||