Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Diabetes Complications / genetics
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Diabetes Complications / metabolism
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Formins
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Humans
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Inflammation / genetics
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Inflammation / metabolism
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Neurodegenerative Diseases / genetics
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Neurodegenerative Diseases / metabolism
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Phosphorylation / physiology
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-akt / chemistry
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Receptor for Advanced Glycation End Products
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Receptors, Immunologic / chemistry
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Signal Transduction / physiology*
Substances
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Adaptor Proteins, Signal Transducing
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DIAPH1 protein, human
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Formins
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Receptor for Advanced Glycation End Products
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Receptors, Immunologic
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Proto-Oncogene Proteins c-akt