tailieunhanh - Báo cáo Y học: GPI-microdomains (membrane rafts) and signaling of the multi-chain interleukin-2 receptor in human lymphoma/leukemia T cell lines

Subunits (a, b and c) of the interleukin-2 receptor complex (IL-2R) are involved in both proliferative and activationinduced cell death (AICD) signaling of T cells. In addition, the signaling b and c chains are shared by other cytokines (. IL-7, IL-9, IL-15). However, the molecular mechanisms responsible for recruiting/sorting the a chains to the signaling chains at the cell surface are not clear. Here we show, in four cell lines of human adult T cell lymphoma/leukemia origin, that the three IL-2R subunits are compartmented together with HLA glycoproteins and CD48 molecules in the plasma membrane, by means of fluorescence resonance. | Eur. J. Biochem. 269 1199-1208 2002 FEBS 2002 GPI-microdomains membrane rafts and signaling of the multi-chain interleukin-2 receptor in human lymphoma leukemia T cell lines Janos Matkó1 5. Andrea Bodnar2 Gvorav Vereb1. László Bene1 Gvorav Vamosi2 IV 4 B B v B M w v B BB BB w BB B B BB BV V Bf B VB V V B w B BB B B Bf w BB B B BB BV V BB B BB V V BB B B B BB B B Geraelv Szentesi1. János Szollosi1 Rezso Gaspar Jr1. Vaclav Horeisi3 Thomas A Waldmann4 Bl and Sandor Damjanovich1 2 1 Department of Biophysics and Cell Biology 2Cell Biophysics Research Group of the Hungarian Academy of Sciences University of Debrecen Health Science Center Debrecen Hungary 3Institute of Molecular Genetics Academy of Sciences of Czeh Republic Prague Czech Republic 4Metabolism Branch National Cancer Institute National Institutes of Health Bethesda MD USA 5Department of Immunology Eotvos Lorand University Budapest Hungary Subunits a b and c of the interleukin-2 receptor complex IL-2R are involved in both proliferative and activation-induced cell death AICD signaling of T cells. In addition the signaling b and c chains are shared by other cytokines . IL-7 IL-9 IL-15 . However the molecular mechanisms responsible for recruiting sorting the a chains to the signaling chains at the cell surface are not clear. Here we show in four cell lines of human adult T cell lymphoma leukemia origin that the three IL-2R subunits are compartmented together with HLA glycoproteins and CD48 molecules in the plasma membrane by means of fluorescence resonance energy transfer FRET confocal microscopy and immunobiochemical techniques. In addition to the b and cc chains constitutively expressed in detergent-resistant membrane fractions DRMs of T cells IL-2Ra CD25 was also found in DRMs independently of its ligand-occupation. Association of CD25 with rafts was also confirmed by its colocal ization with GM-1 ganglioside. Depletion of membrane cholesterol using methyl-b-cyclodextrin substantially reduced co-clustering