| First Author | Kim G | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 397 |
| Issue | 1 | Pages | 100-5 |
| PubMed ID | 20510162 | Mgi Jnum | J:162423 |
| Mgi Id | MGI:4818855 | Doi | 10.1016/j.bbrc.2010.05.075 |
| Citation | Kim G, et al. (2010) Toll-like receptor 4-mediated c-Jun N-terminal kinase activation induces gp96 cell surface expression via AIMP1 phosphorylation. Biochem Biophys Res Commun 397(1):100-5 |
| abstractText | 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. |
