Date of Award

1-1-2011

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Chemistry

Content Description

1 online resource (xii, 154 pages) : illustrations (some color)

Dissertation/Thesis Chair

Alexander Shekhtman

Committee Members

Alexander Shekhtman, Jayanti Pande, Carla Theimer, Charles P Scholes, Marlene Belfort

Keywords

Interactions, NMR, Prokaryotic, Protein, RAGE, Ubiquitin, Nuclear magnetic resonance spectroscopy, Protein-protein interactions, Mycobacterium tuberculosis

Subject Categories

Biochemistry | Chemistry

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, inflammation, and neurodegeneration. The cytoplasmic domain of RAGE, ctRAGE, is critical for RAGE-dependent signal transduction. As the most membrane proximal event, mDia1 binds to ctRAGE and is essential for RAGE ligand-stimulated phosphorylation of AKT and cell proliferation/migration. We show that ctRAGE contains an unusual alpha-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.

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