LIME, a Novel Transmembrane Adaptor Protein, Associates with p56 lck and Mediates T Cell Activation

Eun Mi Hur, Myoungsun Son, Ok Hee Lee, Young Bong Choi, Changwon Park, Hyunsook Lee, Yungdae Yun

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1463-1473
Number of pages11
JournalJournal of Experimental Medicine
Volume198
Issue number10
DOIs
StatePublished - Nov 17 2003

Keywords

  • Immunological synapse
  • Lipid rafts
  • Signal transduction
  • T cell activation
  • T cell receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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