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

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• 作者：Nursamaa Abdoel^a ; ^{nursamaa@yahoo.com} ; Susana Brun^a ; ¹ ; ^{s.brun@ibmc-cnrs.unistra.fr} ; Carmen Bracho^b ; ^{cbracho@ivic.gob.ve} ; Martí ; n A. Rodrí ; guez^a ; ^{martinalbertove@yahoo.com} ; Ana M. Blasini^a ; ^{amblasini@gmail.com}
• 关键词：Linker for activation of T cells ; Systemic lupus erithematosus ; T cell signaling ; Membrane microdomains ; Immunological synapse
• 刊名：Clinical Immunology
• 出版年：2012
• 期刊代码：95_15216616
• 类别：imm
• 出版时间：March, 2012
• 卷：142
• 期：3
• 页码：243-251
• 文件大小：888 K

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 colocalization 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纬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.