Signal Transduction in Receptor for Advanced Glycation End Products (RAGE)

• DOI: 10.1074/jbc.m111.277731
• Publication Date: 2011-12-23T01:38:29Z
• Authors: Vivek Rai; Andres Y. Maldonado; David S. Burz; Sergey Reverdatto; Ann Marie Schmidt; Alexander Shekhtman
• Keywords: Inflammation; 0303 health sciences; Receptor for Advanced Glycation End Products; Formins; Neurodegenerative Diseases; Protein Structure, Secondary; Protein Structure, Tertiary; Diabetes Complications; 03 medical and health sciences; Humans; Phosphorylation; Receptors, Immunologic; Proto-Oncogene Proteins c-akt; Adaptor Proteins, Signal Transducing; Protein Binding; Signal Transduction

The receptor for advanced glycation end products (RAGE) is a multiligand cell surface macromolecule that plays a central role in the etiology of diabetes complications, inflammation, and neurodegeneration. The cytoplasmic domain of RAGE (C-terminal RAGE; ctRAGE) is critical for RAGE-dependent signal transduction. As the most membrane-proximal event, mDia1 binds to ctRAGE, and it is essential for RAGE ligand-stimulated phosphorylation of AKT and cell proliferation/migration. We show that ctRAGE contains an unusual α-turn that mediates the mDia1-ctRAGE interaction and is required for RAGE-dependent signaling. The results establish a novel mechanism through which an extracellular signal initiated by RAGE ligands regulates RAGE signaling in a manner requiring mDia1.