The Journal of Experimental Medicine
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Published online 10 November 2003 doi:10.1084/jem.20030232
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© Rockefeller University Press, 0022-1007/2003/11/1463 $5.00
The Journal of Experimental Medicine, Volume 198, Number 10, 1463-1473

LIME, a Novel Transmembrane Adaptor Protein, Associates with p56lck and Mediates T Cell Activation

Eun Mi Hur2, Myoungsun Son1, Ok-Hee Lee1, Young Bong Choi1, Changwon Park1, Hyunsook Lee1 and Yungdae Yun1,2

1 The Division of Molecular Life Science and Center for Cell Signaling Research at Ewha Woman's University, 120-750 Seoul, Korea
2 Signal Transduction Laboratory, Mogam Biotechnology Research Institute, Koosungmyon, Yonginsi, Kyunggido 449-910, Korea

Address correspondence to Yungdae Yun, Div. of Molecular Life Science, Ewha Woman's University, 11-1 Daehyundong, Seodaemungu, 120-750 Seoul, Korea. Phone: 822-3277-3248; Fax: 822-3277-3760; email: YUNYUNG{at}ewha.ac.kr; or HyunSook Lee, Div. of Molecular Life Science, Ewha Woman's University, 11-1 Daehyundong, Seodaemungu, 120-750 Seoul, Korea. Phone: 822-3277-4335; Fax: 822-3277-3760; email: hyunlee{at}ewha.ac.kr

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.

Key Words: T cell receptor • signal transduction • lipid rafts • immunological synapse • T cell activation


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