CDB15:0000774 HSP90B1 — TLR4

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway.

The Journal of biological chemistry, 2002; PubMed, Homo sapiens HSP90B1 — Homo sapiens TLR4

ABSTRACT: The heat shock protein Gp96 has been shown to induce specific immune responses. On one hand, this phenomenon is based on the specific interaction with CD91 that mediates endocytosis and results in major histocompatibility complex class I-restricted representation of the Gp96-associated peptides. On the other hand, Gp96 induces activation of professional antigen-presenting cells, resulting in the production of pro-inflammatory cytokines and up-regulation of costimulatory molecules by unknown mechanisms. In this study, we have analyzed the consequences of Gp96 interaction with cells expressing different Toll-like receptors (TLRs) and with bone marrow-derived dendritic cells from mice lacking functional TLR2 and/or TLR4 molecules. We find that the Gp96-TLR2/4 interaction results in activation of nuclear factor kappaB-driven reporter genes and mitogen- and stress-activated protein kinases and induces IkappaBalpha degradation. Bone marrow-derived dendritic cells of C3H/HeJ and more pronounced C3H/HeJ/TLR2(-/-) mice fail to respond to Gp96. Interestingly, activation of bone marrow-derived dendritic cells depends on endocytosis of Gp96 molecules. Our results provide, for the first time, the molecular basis for understanding the Gp96-mediated activation of antigen-presenting cells by describing the simultaneous stimulation of the innate and adaptive immune system. This feature explains the remarkable ability of Gp96 to induce specific immune responses against tumors and pathogens.

Basic Information on HSP90B1

Ligand Name: heat shock protein 90 beta family member 1

Other Symbols: TRA1, GP96, GRP94

Ligand Location: cell membrane based on perplexity

HGNC Gene Symbol Report: HSP90B1

GeneCards: HSP90B1

HGNC Gene Group: MicroRNA host genes, Heat shock proteins

Functional Annotations for HSP90B1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for HSP90B1

HSP90B1 — LRP1 ・ HSP90B1 — TLR2 ・ HSP90B1 — LY96 ・ HSP90B1 — SCARF1

Basic Information on TLR4

Receptor Name: toll like receptor 4

Other Symbols: hToll, CD284, TLR-4, ARMD10

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: TLR4

GeneCards: TLR4

HGNC Gene Group: TIR domain containing, CD molecules

Functional Annotations for TLR4

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for TLR4

BGN — TLR4 ・ DEFB4A — TLR4 ・ HSPA1A — TLR4 ・ S100A8 — TLR4 ・ S100A9 — TLR4 ・ SFTPD — TLR4 ・ ZG16B — TLR4 ・ DCN — TLR4 ・ FGA — TLR4 ・ FGB — TLR4 ・ FGG — TLR4 ・ PRG4 — TLR4 ・ AHSG — TLR4 ・ ANXA2 — TLR4 ・ CCN1 — TLR4 ・ CIRBP — TLR4 ・ CXCL10 — TLR4 ・ FCN2 — TLR4 ・ HMGB1 — TLR4 ・ HP — TLR4 ・ HSPA4 — TLR4 ・ LGALS9 — TLR4 ・ MMP9 — TLR4 ・ NAMPT — TLR4 ・ RBP4 — TLR4 ・ RETN — TLR4 ・ S100A1 — TLR4 ・ S100A12 — TLR4 ・ S100A4 — TLR4 ・ SAA1 — TLR4 ・ SFTPA1 — TLR4 ・ TNC — TLR4 ・ WNT5A — TLR4