Linker for activation of T cells is displaced from lipid rafts and decreases in lupus T cells after activation via the TCR/CD3 pathway

被引：13
作者：
Abdoel, Nursamaa [1 ]
Brun, Susana [1 ]
Bracho, Carmen [2 ]
Rodriguez, Martin A. [1 ]
Blasini, Ana M. [1 ]
机构：
[1] Cent Univ Venezuela, Ctr Nacl Enfermedades Reumat, Div Rheumatol, Hosp Univ Caracas, Caracas, Venezuela
[2] Inst Venezolano Invest Cient, Ctr Microbiol & Biol Celular, Altos De Pipe, Edo Miranda, Venezuela
来源：
CLINICAL IMMUNOLOGY | 2012年 / 142卷 / 03期
关键词：
Linker for activation of T cells; Systemic lupus erithematosus; T cell signaling; Membrane microdomains; Immunological synapse; SIGNAL-TRANSDUCTION; IMMUNOLOGICAL SYNAPSE; MEMBRANE DOMAINS; PROTEIN-KINASES; ZETA-CHAIN; TCR-ZETA; ERYTHEMATOSUS; LAT; LYMPHOCYTES; EXPRESSION;
D O I：
10.1016/j.clim.2011.12.010
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Systemic lupus erythematosus (SLE) is characterized by abnormal signal transduction mechanisms in T lymphocytes. Linker for activation of T cells (LAT) couples TCR/CD3 activation with downstream signaling pathways. We reported diminished ERK 1/2 kinase activity in TCR/CD3 stimulated lupus T cells. In this study we evaluated the expression, phosphorylation, lipid raft and immunological synapse (IS) localization and colocatization of LAT with key signalosome molecules. We observed a diminished expression and an abnormal localization of LAT in lipid rafts and at the IS in activated lupus T cells. LAT phosphorylation, capture by GST-Grb2 fusion protein, and coupling to Grb2 and PLC gamma 1, was similar in healthy control and lupus T cells. Our results suggest that an abnormal localization of LAT within lipid rafts and its accelerated degradation after TCR/CD3 activation may compromise the assembly of the LAT signalosome and downstream signaling pathways required for full MAPK activation in lupus T cells. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码：243 / 251
页数：9
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