FEBS Letters | |
The receptor for advanced glycation end‐products (RAGE) directly binds to ERK by a D‐domain‐like docking site | |
Tsutsumi, Kae1  Ishihara, Katsuya1  Kawane, Shiho1  Nakajima, Motowo1  Kasaoka, Tatsuhiko1  | |
[1] Discovery Biology, Tsukuba Research Institute, Novartis Pharma K.K., Okubo 8, Tsukuba-shi, Ibaraki 300-2611, Japan | |
关键词: Receptor for advanced glycation end-products; Extracellular signal-regulated kinase; Amphoterin; ERK; extracellular signal-regulated kinase; AGE; advanced glycation end-product; RAGE; receptor for AGE; MAPK; mitogen-activated protein kinase; RSK; ribosomal S6 kinase; MnK; MAPK-interacting kinase; MSK; mitogen- and stress-activated protein kinase; 2D-PAGE; two-dimensional polyacrylamide gel electrophoresis; | |
DOI : 10.1016/S0014-5793(03)00846-9 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
The receptor for advanced glycation end-products (RAGE)-mediated cellular activation through the mitogen-activated protein kinase (MAPK) cascade, activation of NF-κB and Rho family small G-proteins, cdc42/Rac, is implicated in the pathogenesis of inflammatory disorders and tumor growth/metastasis. However, the precise molecular mechanisms for the initiation of cell signaling by RAGE remain to be elucidated. In this study, proteins which directly bind to the cytoplasmic C-terminus of RAGE were purified from rat lung extracts using an affinity chromatography technique and identified to be extracellular signal-regulated protein kinase-1 and -2 (ERK-1/2). Their interactions were confirmed by immunoprecipitation of ERK-1/2 from RAGE-expressing HT1080 cell extracts with anti-RAGE antibody. Furthermore, the augmentation of kinase activity of RAGE-bound ERK upon the stimulation of cells with amphoterin was demonstrated by determining the phosphorylation level of myelin basic protein, an ERK substrate. In vitro binding studies using a series of C-terminal deletion mutants of human RAGE revealed the importance of the membrane-proximal cytoplasmic region of RAGE for the direct ERK–RAGE interaction. This region contained a sequence similar to the D-domain, a ERK docking site which is conserved in some ERK substrates including MAPK-interacting kinase-1/2, mitogen- and stress-activated protein kinase-1, and ribosomal S6 kinase. These data suggest that ERK may play a role in RAGE signaling through direct interaction with RAGE.
【 授权许可】
Unknown
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