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Interleukin-11 receptor alpha subunit (IL-11Rα) and glycoprotein 130 (gp130) receptor complex (IL-11Rα/gp130)

Target: IL-11Rα/gp130
Molecular classification: Receptor, Type I cytokine receptor family (IL-11Rα), Signal transducing receptor (gp130), Cell surface protein

Overview

The IL-11Rα/gp130 complex is a heterodimeric cell surface receptor for the cytokine interleukin-11. IL-11 first binds to the IL-11Rα subunit, forming a high-affinity binary complex, which then recruits the signal transducing subunit gp130 (also known as IL6ST) to form a signaling ternary complex. This complex triggers downstream pathways, primarily JAK/STAT (especially STAT3), ERK/MAPK, and PI3K, mediating functions such as cellular proliferation, differentiation, immune response modulation, and regulation of fibrotic processes[1][2][3][7][9]. The IL-11Rα/gp130 signaling axis is implicated in cancer, fibrosis, inflammation, and neurodegenerative diseases, and is a therapeutic target for antibody and protein-based drugs that block IL-11 mediated signaling, as well as for functional studies in bone metabolism and myelination[2][3][4][6].

Other names: IL-11 receptor alpha subunitInterleukin-11 receptor alphagp130 (also known as IL6ST, glycoprotein 130)IL11RA (gene symbol for IL-11Rα)IL6ST (gene symbol for gp130)IL-11 receptor complex

Mechanism of action

Antibody-mediated inhibition of IL-11 binding to IL-11Rα, preventing complex formation with gp130, and resultant downstream signaling block; Inhibition of JAK/STAT activation (particularly STAT3/STAT1); Inhibition of ERK/MAPK and PI3K signaling pathways

Biological functions

Signal transductionCell proliferationImmune responseRegulation of inflammationRegulation of bone metabolism and homeostasisRemyelination (nervous system)Fibrosis regulation

Disease associations

Cancer (various solid tumors and hematologic malignancies)Fibrosis (e.g., cardiac, hepatic, pulmonary)InflammationNeurodegenerative disease (multiple sclerosis, through remyelination)Cardiovascular disease

Safety considerations

Ubiquitous expression of gp130 can increase the risk of off-target effects and systemic toxicityPotential for unintended immune modulation, resulting in immunosuppression or inflammationRole in normal bone metabolism and tissue homeostasis, raising possible adverse effects on bone or fibrosis in non-target tissuesUnknown long-term effects on remyelination and nervous system function

Interacting drugs

9MW3811 (investigational monoclonal antibody against IL-11)

3 more in the full profile.

Biomarkers

pSTAT3 (phosphorylated STAT3)pERK (phosphorylated ERK)IL-11 and IL-11Rα expression levels (tumor or tissue biopsy)XCL1 and CCL7 levels in immune microenvironment (preclinically)

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