LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activation.
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.
Hur
Eun Mi
EM
Div. of Molecular Life Science, Ewha Woman's University, 11-1 Daehyundong, Seodaemungu, 120-750 Seoul, Korea.
Son
Myoungsun
M
Lee
Ok-Hee
OH
Choi
Young Bong
YB
Park
Changwon
C
Lee
Hyunsook
H
Yun
Yungdae
Y
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D033942:Adaptor Proteins, Vesicular Transport; D018076:DNA, Complementary; C480489:Lck-interacting protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases