Toll-like receptor 4-mediated c-Jun N-terminal kinase activation induces gp96 cell surface expression via AIMP1 phosphorylation

Gyuyoup Kim, Jung Min Han, Sunghoon Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The presentation of the endoplasmic reticulum resident chaperone protein, gp96 on the cell surface have been considered as a phenomenon of the immunogenic process activation. Previously, we showed aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) can form a molecular complex with gp96, regulate the ER retention of gp96 through KDEL receptor, and suppress its cell surface expression. However, the physiological conditions that modulate AIMP1-gp96 interaction and cell surface expression of gp96 are not known. In this study, we investigated the process that which can modulate dissociation of AIMP1 and gp96 by using Toll-like receptor (TLR) activation. MyD88 pathway by LPS-mediated TLR4 activation induced the cell surface presentation of gp96 through c-Jun N-terminal kinase (JNK). AIMP1 was phosphorylated by JNK upon LPS stimulation and gp96 was dissociated from phosphorylated AIMP1. We further demonstrated that serine-140 residue of AIMP1 was phosphorylated by JNK and alanine mutation of serine-140 suppressed LPS-induced cell surface expression of gp96. Altogether, these results suggest that AIMP1 is phosphorylated by JNK through TLR-MyD88 pathway and lose the regulatory activity for ER retention of gp96, resulting in the increase of cell surface expression of gp96, and provide a new molecular mechanism underlying TLR-mediated gp96 regulation.

Original languageEnglish
Pages (from-to)100-105
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume397
Issue number1
DOIs
Publication statusPublished - 2010 Jun 18

Fingerprint

Amino Acyl-tRNA Synthetases
Toll-Like Receptor 4
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Chemical activation
Toll-Like Receptors
Proteins
Serine
Cell Communication
Endoplasmic Reticulum
Alanine
Mutation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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abstract = "The presentation of the endoplasmic reticulum resident chaperone protein, gp96 on the cell surface have been considered as a phenomenon of the immunogenic process activation. Previously, we showed aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) can form a molecular complex with gp96, regulate the ER retention of gp96 through KDEL receptor, and suppress its cell surface expression. However, the physiological conditions that modulate AIMP1-gp96 interaction and cell surface expression of gp96 are not known. In this study, we investigated the process that which can modulate dissociation of AIMP1 and gp96 by using Toll-like receptor (TLR) activation. MyD88 pathway by LPS-mediated TLR4 activation induced the cell surface presentation of gp96 through c-Jun N-terminal kinase (JNK). AIMP1 was phosphorylated by JNK upon LPS stimulation and gp96 was dissociated from phosphorylated AIMP1. We further demonstrated that serine-140 residue of AIMP1 was phosphorylated by JNK and alanine mutation of serine-140 suppressed LPS-induced cell surface expression of gp96. Altogether, these results suggest that AIMP1 is phosphorylated by JNK through TLR-MyD88 pathway and lose the regulatory activity for ER retention of gp96, resulting in the increase of cell surface expression of gp96, and provide a new molecular mechanism underlying TLR-mediated gp96 regulation.",
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Toll-like receptor 4-mediated c-Jun N-terminal kinase activation induces gp96 cell surface expression via AIMP1 phosphorylation. / Kim, Gyuyoup; Han, Jung Min; Kim, Sunghoon.

In: Biochemical and Biophysical Research Communications, Vol. 397, No. 1, 18.06.2010, p. 100-105.

Research output: Contribution to journalArticle

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