The 1.5 Å crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding.

Park, HaJeung; Adsit, Floyd G.; Boyington, Jeffrey C.

doi:10.1074/jbc.a110.169276

Cited by 6 publications

(7 citation statements)

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“…The interaction between RAGE and TLR9 is required for HMGB1-nDNA complex and TFAM-mitDNA complex-mediated immune responses (139,140). RAGE also has the ability to directly recognize DNA (141). A study indicates that besides RAGE and TLR9, TLR2 is required for the HMGB1-nucleosome complexmediated immune response in macrophages and dendritic cells (142).…”

Section: Dna and Acute Pancreatitismentioning

confidence: 99%

Cell Death and DAMPs in Acute Pancreatitis

Kang

Lotze

Zeh

et al. 2014

Mol Med

129

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The pancreas is a dual-purpose gland with exocrine and endocrine functions. The exocrine pancreas produces digestive proteases in inactive proenzyme form, namely zymogens. The pancreas is normally able to protect itself from zymogen activation by synthesis of protease inhibitors such as pancreatic secretory trypsin inhibitor and serine protease inhibitor (for example, SPINK1/Spink3). By contrast, pancreatic autodigestion and subsequent AP is initiated once these defenses are impaired. In studies of rodent models (for example, repetitive cerulein or L-arginine injections, choline-deficient ethionine supplementation [CDE] diet, perfusion of taurocholate into the biliary or pancreatic duct and surgical ligation or infusion of pancreatic duct models), some essential pathogenic AP events have been identified (see Figure 1) (15,16).The development of AP involves a complex cascade of events (17), which start with injury or disruption of the pan- Cell Death and DAMPs in Acute PancreatitisRui Kang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, and Daolin Tang Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP . Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP . DAMPs might be an attractive therapeutic target in AP.

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Section: Dna and Acute Pancreatitismentioning

confidence: 99%

Cell Death and DAMPs in Acute Pancreatitis

Kang

Lotze

Zeh

et al. 2014

Mol Med

129

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“…, RAGE was crystallized, and x-ray crystallography revealed an elongated molecule with a large positively charged region on the surface with direct implications for the binding of ligands (37,38). Based on these observations, to assess whether the basic amino acid regions on the surface of RAGE interacted with GAGs, ELISA was performed using two chemically synthesized peptides (Cys-38 -Ala-60 and Gly-94 -Tyr-117) that contain basic amino acids and the antisera raised against these peptides.…”

Section: Binding Region On Rage With Cs-e and Heparin And Minimal Sizmentioning

confidence: 99%

Receptor for Advanced Glycation End Products (RAGE) Functions as Receptor for Specific Sulfated Glycosaminoglycans, and Anti-RAGE Antibody or Sulfated Glycosaminoglycans Delivered in Vivo Inhibit Pulmonary Metastasis of Tumor Cells

Mizumoto¹,

Takahashi²,

Sugahara

2012

Journal of Biological Chemistry

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“…The V domain of RAGE, which is the major contributor to ligand "binding", is positively charged [5,[77][78][79][80]. This positive charge extends far enough and renders RAGE an electrostatic trap for its negatively charged ligands [5,77,[79][80][81][82]. Also, there is strong evidence that RAGE interacts with the negatively charged patches of AGE-modified proteins [5,79,80].…”

Section: The Role Of Rage In Lung Physiologymentioning

confidence: 96%

“…This positive charge extends far enough and renders RAGE an electrostatic trap for its negatively charged ligands [5,77,[79][80][81][82]. Also, there is strong evidence that RAGE interacts with the negatively charged patches of AGE-modified proteins [5,79,80]. In addition, electrostatic charge modifications alter RAGE-ligand interactions and downstream cell signaling pathways, affecting major cell functions such as adhesion, migration and proliferation [81,82].…”

Section: The Role Of Rage In Lung Physiologymentioning

confidence: 99%

“…Also, a large body of evidence shows that the living organisms from cells to humans possess a huge spectrum of receptors (photoreceptors) that are able to efficiently receive electromagnetic fields (signals). The V domain of RAGE, which is the major contributor to ligand "binding", is positively charged [5,[77][78][79][80]. This positive charge extends far enough and renders RAGE an electrostatic trap for its negatively charged ligands [5,77,[79][80][81][82].…”

Section: The Role Of Rage In Lung Physiologymentioning

confidence: 99%

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Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?

Marinakis

Bagkos

Piperi

et al. 2014

Clinical Chemistry and Laboratory Medicine (CCLM)

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Lung cancer is one of the most common malignancies in the world and one of the leading causes of death from cancer. In the search for molecules that may be involved in lung tumor induction and progression, the receptor of advanced glycation end products (RAGE) comes across as a critical regulator of lung physiology. RAGE is a multiligand receptor that presents a differential expression pattern in lung epithelial cells compared to other cell types being gradually increased from fetal to birth and adult life. Under stress conditions, RAGE expression and activation are rapidly elevated resulting in chronic inflammation, which, in turn, in many instances, promotes epithelial cell malignant transformation. RAGE overexpression in normal lung alveolar type I epithelial cells is followed by rapid downregulation upon malignant transformation, being associated with increased aggressiveness. This is a striking paradox, since in every other cell type the pattern of RAGE expression follows the opposite direction, suggesting the involvement of RAGE in the well-functioning of lung cells. Additionally, RAGE has been attributed with the role of adhesion molecule, since it can stabilize mature alveolar epithelial cells to their substrate (basal lamina) by interacting electrostatically with other molecules. However, the reduction of RAGE observed in lung tumorigenesis interrupts cell-to-cell and cell-to-substrate communication, which is a critical step for cancer cell induction, progression and migration. This review addresses the differential properties of RAGE in lung physiology and carcinogenesis, providing evidence of therapeutic possibilities.

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The 1.5 Å crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding.

Cited by 6 publications

References 0 publications

Cell Death and DAMPs in Acute Pancreatitis

Cell Death and DAMPs in Acute Pancreatitis

Receptor for Advanced Glycation End Products (RAGE) Functions as Receptor for Specific Sulfated Glycosaminoglycans, and Anti-RAGE Antibody or Sulfated Glycosaminoglycans Delivered in Vivo Inhibit Pulmonary Metastasis of Tumor Cells

Critical role of RAGE in lung physiology and tumorigenesis: a potential target of therapeutic intervention?

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