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

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.
Mesh Terms:
Antigens, Neoplasm, Cell Membrane, Cytokines, Endoplasmic Reticulum, Enzyme Activation, HL-60 Cells, Humans, Immunity, Innate, JNK Mitogen-Activated Protein Kinases, Lipopolysaccharides, Molecular Chaperones, Mutation, Myeloid Differentiation Factor 88, Neoplasm Proteins, Phosphorylation, RNA-Binding Proteins, Serine, Toll-Like Receptor 4
Biochem. Biophys. Res. Commun.
Date: Jun. 18, 2010
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