title: Critical role of lipid rafts in CD154-mediated T cell signaling.
abstract: Although signal pathways triggered via the CD40 molecule are well characterized, those induced via CD154 are less known. This study demonstrates that engagement of CD154 in Jurkat D1.1 cells with soluble CD40 leads to PKC alpha and delta activation, calcium mobilization, and phosphorylation of the Map kinases ERK1/2 and p38. Such response is accompanied by significant recruitment of CD154 into lipid rafts. Disruption of lipid rafts integrity with nystatin or methyl beta-cyclodextrin abrogated PKCalpha PKCdelta and p38 phosphorylation, but had no effect on ERK1/2 phosphorylation. Inhibition of PKC activation completely abolished p38 phosphorylation but had no effect on ERK1/2 phosphorylation, suggesting that localization of CD154 within lipid rafts is an absolute requirement for CD154-induced PKCalpha- and PKCdelta-dependent p38 phosphorylation. Furthermore, CD154 acts as co-stimulator for the production of IL-2 in an APC-superantigen-T-cell activation model. The results obtained demonstrate for the first time, that lipid rafts are of immunological relevance for CD154-triggered signals, and reinforce the importance of CD154 in T-cell activation.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Saint Luc, Montréal, Que., Canada H2X 1P1.
authors.forename: Youssef
authors.initials: Y
authors.lastname: El Fakhry
authors.forename: Haydar
authors.initials: H
authors.lastname: Alturaihi
authors.forename: Djibril
authors.initials: D
authors.lastname: Diallo
authors.forename: Yehye
authors.initials: Y
authors.lastname: Merhi
authors.forename: Walid
authors.initials: W
authors.lastname: Mourad
mesh_terms: D015153:Blotting, Western; D023201:CD40 Ligand / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D021962:Membrane Microdomains / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D023201:CD40 Ligand