LIME, a novel transmembrane adaptor protein, associates with p561ck and mediates T cell activation

被引:81
作者
Hur, EM
Son, M
Lee, OH
Choi, LB
Park, C
Lee, H
Yun, YD
机构
[1] Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea
[2] Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea
[3] Mogam Biotechnol Res Inst, Signal Transduct Lab, Yonginsi 449910, Kyunggido, South Korea
关键词
T cell receptor; signal transduction; lipid rafts; immunological synapse; T cell activation;
D O I
10.1084/jem.20030232
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this study, we identify and characterize a novel transmembrane adaptor protein, designated Lck-interacting membrane protein (LIME), as a binding partner of the Lck Src homology (SH)2 domain. LIME possesses a short extracellular domain, a transmembrane domain, and a cytoplasmic tail containing five tyrosine-based motifs. The protein is primarily expressed in hematopoietic cells and lung. Interestingly, LIME expression is up-regulated by TCR stimulation and sustained up to 24 h, suggesting that LIME acts throughout the early to late stages of T cell activation. LIME is localized to membrane rafts and distributed within the T cell-APC contact site. Upon TCR stimulation of Jurkat T cells, LIME associates with Lck as a tyrosine-phosphorylated protein. Experiments using Jurkat T cells expressing CD8-LIME chimera reveal that the protein associates with phosphatidylinositol 3-kinase, Grb2, Gads, and SHP2, and activates ERK1/2 and JNK but not p38. Moreover, overexpression of LIME in Jurkat T cells induces transcriptional activation of the IL-2 promoter. Our data collectively show that LIME is a raft-associated transmembrane adaptor protein linking TCR stimuli to downstream signaling pathways via associations with Lck.
引用
收藏
页码:1463 / 1473
页数:11
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