Molecular Mechanisms of Peptide Loading by the Tumor Rejection Antigen/Heat Shock Chaperone gp96 (GRP94)

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Biophysical analysis of the endoplasmic reticulum-resident chaperone/heat shock protein gp96/GRP94 and its complex with peptide antigen.

Animals vaccinated with heat shock protein (HSP)--peptide complexes develop specific protective immunity against cancers from which the HSPs were originally isolated. This autologous specific immunity has been demonstrated using a number of HSP--peptide antigen complexes. A prototypical HSP-based cancer vaccine is the gp96--peptide antigen complex, which is currently undergoing human clinical t...

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PLATELETS AND THROMBOPOIESIS Heat-shock protein gp96/grp94 is an essential chaperone for the platelet glycoprotein Ib-IX-V complex

1Center for Immunotherapy of Cancer and Infectious Diseases, Department of Immunology, University of Connecticut School of Medicine, Farmington, CT; 2Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC; 3Lea’s Foundation Center for Hematological Disorders, University of Connecticut School of Medicine, Farmington, CT; and 4Department of Pharmacology, Uni...

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Heat-shock protein gp96/grp94 is an essential chaperone for the platelet glycoprotein Ib-IX-V complex.

The platelet glycoprotein Ib-IX-V complex (GPIb-IX-IV) is the receptor for VWF and is responsible for VWF-mediated platelet activation and aggregation. Loss of the GPIb-IX-V complex is pathogenic for Bernard-soulier Syndrome (BSS), which is characterized by macrothrombocytopenia and impaired platelet function. It remains unclear how the GPIb-IX-V complex is assembled and whether there is a role...

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GRP94/gp96 elicits ERK activation in murine macrophages. A role for endotoxin contamination in NF-kappa B activation and nitric oxide production.

Vaccination of mice with GRP94/gp96, the endoplasmic reticulum Hsp90, elicits a variety of immune responses sufficient for tumor rejection and the suppression of metastatic tumor progression. Macrophages are a prominent GRP94/gp96 target, with GRP94/gp96 reported to activate macrophage NF-kappa B signaling and nitric oxide production, as well as the MAP kinase p38, JNK, and ERK signaling cascad...

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The molecular chaperone gp96/GRP94 interacts with Toll-like receptors and integrins via its C-terminal hydrophobic domain.

The structural basis for molecular chaperones to discern misfolded proteins has long been an enigma. As the endoplasmic reticulum paralogue of the cytosolic HSP90, gp96 (GRP94, HSP90b1) is an essential molecular chaperone for Toll-like receptors (TLRs) and integrins. However, little is known about its client-binding domain (CBD). Herein, we provide genetic and biochemical evidence to definitive...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 1999

ISSN: 0021-9258

DOI: 10.1074/jbc.274.17.12023