Page last updated: 2024-10-24

interleukin-6 receptor complex

Definition

Target type: cellularcomponent

A hexameric protein complex consisting of two molecules each of interleukin-6, interleukin-6 receptor alpha chain, and gp-130. [PMID:8083235]

The interleukin-6 (IL-6) receptor complex is a multimeric protein complex that plays a crucial role in mediating the signaling of the cytokine IL-6. It is composed of two primary subunits: the IL-6 receptor α-chain (IL-6Rα) and the gp130 transmembrane signaling subunit.

IL-6Rα is a type I transmembrane protein that serves as the specific binding site for IL-6. It is expressed primarily on hepatocytes, but also on other cell types, including immune cells and neurons.

gp130 is a ubiquitously expressed transmembrane protein that is also involved in the signaling of other cytokines, including IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OSM). It is a crucial component of the IL-6 receptor complex, as it is responsible for initiating the downstream signaling cascade.

Upon binding of IL-6 to IL-6Rα, the complex undergoes a conformational change that allows it to associate with gp130. This association results in the formation of a hexameric complex consisting of two IL-6Rα subunits, two gp130 subunits, and two molecules of IL-6.

The formation of the hexameric complex triggers the activation of the Janus kinase (JAK) family of tyrosine kinases, which are associated with the cytoplasmic domains of gp130. The activated JAKs phosphorylate the gp130 subunits, creating docking sites for the signal transducer and activator of transcription (STAT) proteins.

STAT proteins bind to the phosphorylated gp130 subunits and become phosphorylated themselves. The phosphorylated STAT proteins dimerize and translocate to the nucleus, where they act as transcription factors to regulate the expression of target genes involved in various cellular processes, including inflammation, immune responses, cell growth, and differentiation.'
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Proteins (2)

ProteinDefinitionTaxonomy
Interleukin-6 receptor subunit betaAn interleukin-6 receptor subunit beta that is encoded in the genome of human. [PRO:WCB, UniProtKB:P40189]Homo sapiens (human)
Interleukin-6An interleukin-6 that is encoded in the genome of human. [PRO:JAN, UniProtKB:P05231]Homo sapiens (human)

Compounds (4)

CompoundDefinitionClassesRoles
bergeninbergenin: RN refers to (2R-(2alpha,3beta,4alpha,4aalpha,10bbeta))-isomer; structuretrihydroxybenzoic acidmetabolite
madindoline amadindoline A: inhibits interleukin-6; isolated from Streptomyces; structure in first source
bi 653048 bs h3po4BI 653048 BS H3PO4: structure in first source
lmt-28LMT-28: an interleukin-6 inhibitor that binds gp130; structure in first source