Trafficking of LAG-3 to the surface on activated T cells via its cytoplasmic domain and protein kinase C signaling

Joonbeom Bae, Suk Jun Lee, Chung Gyu Park, Youngsik Lee, Taehoon Chun

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18 Citations (Scopus)

Abstract

Lymphocyte activation gene-3 (LAG-3; CD223), a structural homolog of CD4, binds to MHC class II molecules. Recent research indicated that signaling mediated by LAG-3 inhibits T cell proliferation, and LAG-3 serves as a key surface molecule for the function of regulatory T cells. Previous reports demonstrated that the majority of LAG-3 is retained in the intracellular compartments and is rapidly translocated to the cell surface upon stimulation. However, the mechanism by which LAG-3 translocates to the cell surface was unclear. In this study, we examined the trafficking of human LAG-3 under unstimulated as well as stimulated conditions of T cells. Under the unstimulated condition, the majority of LAG-3 did not reach the cell surface, but rather degraded within the lysosomal compartments. After stimulation, the majority of LAG-3 translocated to the cell surface without degradation in the lysosomal compartments. Results indicated that the cytoplasmic domain without Glu-Pro repetitive sequence is critical for the translocation of LAG-3 from lysosomal compartments to the cell surface. Moreover, protein kinase C signaling leads to the translocation of LAG-3 to the cell surface. However, two potential serine phosphorylation sites from the LAG-3 cytoplasmic domain are not involved in the translocation of LAG-3. These results clearly indicate that LAG-3 trafficking from lysosomal compartments to the cell surface is dependent on the cytoplasmic domain through protein kinase C signaling in activated T cells.

Original languageEnglish
Pages (from-to)3101-3112
Number of pages12
JournalJournal of Immunology
Volume193
Issue number6
DOIs
Publication statusPublished - 2014 Jan 1

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Protein Kinase C
T-Lymphocytes
Human Trafficking
Nucleic Acid Repetitive Sequences
Regulatory T-Lymphocytes
Lymphocyte Activation
Serine
Phosphorylation
Cell Proliferation
Research
Genes

ASJC Scopus subject areas

  • Immunology

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Trafficking of LAG-3 to the surface on activated T cells via its cytoplasmic domain and protein kinase C signaling. / Bae, Joonbeom; Lee, Suk Jun; Park, Chung Gyu; Lee, Youngsik; Chun, Taehoon.

In: Journal of Immunology, Vol. 193, No. 6, 01.01.2014, p. 3101-3112.

Research output: Contribution to journalArticle

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