RAGE receptor binding

Definition

Target type: molecularfunction

Binding to a RAGE receptor, the receptor for advanced glycation end-products. [GOC:ai]

RAGE (Receptor for Advanced Glycation End products) is a multi-ligand receptor that plays a critical role in the recognition and binding of a diverse array of ligands, including advanced glycation end products (AGEs), S100/calgranulin proteins, amyloid-beta peptides, and high-mobility group box 1 (HMGB1) protein. These ligands are associated with various pathological conditions such as diabetes, inflammation, neurodegenerative diseases, and cancer.

RAGE receptor binding initiates a complex signaling cascade that involves the activation of downstream signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway, the nuclear factor-kappa B (NF-κB) pathway, and the p38 MAPK pathway. These pathways, in turn, regulate the expression of pro-inflammatory cytokines, chemokines, and adhesion molecules, contributing to the pathogenesis of various diseases.

Specifically, RAGE binding to its ligands leads to the activation of intracellular signaling molecules such as Ras, Rac, and Rho GTPases. These molecules activate downstream effector kinases, including the MAPK kinases (MEK) and the p38 MAPK kinases (MKK). MEK and MKK, in turn, activate the MAPK cascade, leading to the phosphorylation and activation of transcription factors such as c-Jun, c-Fos, and Elk-1. These transcription factors bind to specific DNA sequences, resulting in the expression of genes involved in inflammatory processes, cell growth, and survival.

Furthermore, RAGE activation also triggers the NF-κB pathway, which is a key regulator of inflammatory responses. Binding of RAGE ligands leads to the recruitment of adaptor proteins, such as TRAF6, which activate the IκB kinase (IKK) complex. IKK phosphorylates the inhibitor of NF-κB (IκB), leading to its ubiquitination and proteasomal degradation. This degradation releases NF-κB, which translocates to the nucleus and activates the transcription of genes encoding pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6.

RAGE binding to its ligands can also activate the p38 MAPK pathway, which is involved in cell stress responses and inflammatory signaling. Activation of the p38 MAPK pathway leads to the phosphorylation of downstream targets, including transcription factors, kinases, and phosphatases. This phosphorylation event regulates the expression of genes involved in inflammation, cell survival, and apoptosis.

In summary, RAGE receptor binding plays a crucial role in mediating the cellular response to a diverse array of ligands, triggering a complex signaling cascade that orchestrates inflammation, cell growth, and survival. The activation of various downstream signaling pathways, including the MAPK, NF-κB, and p38 MAPK pathways, contribute to the pathogenesis of multiple diseases, highlighting the significance of RAGE signaling in health and disease.'
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Proteins (4)

Compounds (18)