JaLCDOI 10.18926/AMO/55582
FullText URL 71_6_459.pdf
Author Sakaguchi, Masakiyo| Kinoshita, Rie| Endy Widya Putranto| I Made Winarsa Ruma| I Wayan Sumardika| Youyi, Chen| Tomonobu, Naoko| Yamamoto, Ken-ichi| Murata, Hitoshi|
Abstract The receptor for advanced glycation end products (RAGE) is involved in inflammatory pathogenesis. It functions as a receptor to multiple ligands such as AGEs, HMGB1 and S100 proteins, activating multiple intracellular signaling pathways with each ligand binding. The molecular events by which ligand-activated RAGE controls diverse signaling are not well understood, but some progress was made recently. Accumulating evidence revealed that RAGE has multiple binding partners within the cytoplasm and on the plasma membrane. It was first pointed out in 2008 that RAGE’s cytoplasmic tail is able to recruit Diaphanous-1 (Dia-1), resulting in the acquisition of increased cellular motility through Rac1/Cdc42 activation. We also observed that within the cytosol, RAGE’s cytoplasmic tail behaves similarly to a Toll-like receptor (TLR4)-TIR domain, interacting with TIRAP and MyD88 adaptor molecules that in turn activate multiple downstream signals. Subsequent studies demonstrated the presence of an alternative adaptor molecule, DAP10, on the plasma membrane. The coupling of RAGE with DAP10 is critical for enhancing the RAGE-mediated survival signal. Interestingly, RAGE interaction on the membrane was not restricted to DAP10 alone. The chemotactic G-protein-coupled receptors (GPCRs) formyl peptide receptors1 and 2 (FPR1 and FPR2) also interacted with RAGE on the plasma membrane. Binding interaction between leukotriene B4 receptor 1 (BLT1) and RAGE was also demonstrated. All of the interactions affected the RAGE signal polarity. These findings indicate that functional interactions between RAGE and various molecules within the cytoplasmic area or on the membrane area coordinately regulate multiple ligand-mediated RAGE responses, leading to typical cellular phenotypes in several pathological settings. Here we review RAGE’s signaling diversity, to contribute to the understanding of the elaborate functions of RAGE in physiological and pathological contexts.
Keywords receptor for advanced glycation end products RAGE adaptor protein signal transduction inflammatory pathogenesis
Amo Type Review
Published Date 2017-12
Publication Title Acta Medica Okayama
Volume volume71
Issue issue6
Publisher Okayama University Medical School
Start Page 459
End Page 465
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2017 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 29276218