Signal diversity of receptor for advanced glycation end products

Masakiyo Sakaguchi, Rie Kinoshita, Endy Widya Putranto, I. Made Winarsa Ruma, I. Wayan Sumardika, Chen Youyi, Naoko Tomonobu, Ken-ichi Yamamoto, Hitoshi Murata

Research output: Contribution to journalReview article

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)459-465
Number of pages7
JournalActa Medica Okayama
Volume71
Issue number6
Publication statusPublished - Jan 1 2017

Fingerprint

Cell membranes
Ligands
Cell Membrane
Molecules
Advanced Glycosylation End Product-Specific Receptor
Leukotriene B4 Receptors
HMGB1 Protein
Membranes
S100 Proteins
Toll-Like Receptors
Sexual Partners
G-Protein-Coupled Receptors
Cytosol
Cytoplasm
Chemical activation
Phenotype
Peptides
Survival

Keywords

  • Adaptor protein
  • Inflammatory pathogenesis
  • RAGE
  • Receptor for advanced glycation end products
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sakaguchi, M., Kinoshita, R., Putranto, E. W., Ruma, I. M. W., Sumardika, I. W., Youyi, C., ... Murata, H. (2017). Signal diversity of receptor for advanced glycation end products. Acta Medica Okayama, 71(6), 459-465.

Signal diversity of receptor for advanced glycation end products. / Sakaguchi, Masakiyo; Kinoshita, Rie; Putranto, Endy Widya; Ruma, I. Made Winarsa; Sumardika, I. Wayan; Youyi, Chen; Tomonobu, Naoko; Yamamoto, Ken-ichi; Murata, Hitoshi.

In: Acta Medica Okayama, Vol. 71, No. 6, 01.01.2017, p. 459-465.

Research output: Contribution to journalReview article

Sakaguchi, M, Kinoshita, R, Putranto, EW, Ruma, IMW, Sumardika, IW, Youyi, C, Tomonobu, N, Yamamoto, K & Murata, H 2017, 'Signal diversity of receptor for advanced glycation end products', Acta Medica Okayama, vol. 71, no. 6, pp. 459-465.
Sakaguchi M, Kinoshita R, Putranto EW, Ruma IMW, Sumardika IW, Youyi C et al. Signal diversity of receptor for advanced glycation end products. Acta Medica Okayama. 2017 Jan 1;71(6):459-465.
Sakaguchi, Masakiyo ; Kinoshita, Rie ; Putranto, Endy Widya ; Ruma, I. Made Winarsa ; Sumardika, I. Wayan ; Youyi, Chen ; Tomonobu, Naoko ; Yamamoto, Ken-ichi ; Murata, Hitoshi. / Signal diversity of receptor for advanced glycation end products. In: Acta Medica Okayama. 2017 ; Vol. 71, No. 6. pp. 459-465.
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