Insulin-like growth factor-binding protein 3 receptor (IGFBP-3R)

The Insulin-like growth factor-binding protein 3 receptor (IGFBP-3R), also known as TMEM219, is a 240-amino acid transmembrane protein that mediates the IGF-independent biological activities of IGFBP-3 (Ingermann et al., 2010). It functions primarily as a pro-apoptotic receptor, triggering the caspase-8 signaling pathway upon ligand binding to inhibit cell growth and induce programmed cell death (UniProt Q86XT9). In the context of oncology, IGFBP-3R is frequently characterized as a tumor suppressor, with reduced expression levels observed in several cancers, including breast, prostate, and lung malignancies (Lee et al., 2014). Beyond cancer, the receptor plays a significant role in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), where it contributes to airway hyperresponsiveness and epithelial cell death (Kim et al., 2018). Research into the IGFBP-3/IGFBP-3R axis has identified it as a potential therapeutic target, with studies exploring the use of recombinant IGFBP-3 or receptor agonists to suppress tumor growth. However, the dual role of this receptor in different pathologies—promoting beneficial apoptosis in tumors while contributing to detrimental tissue remodeling in inflammatory diseases—presents a significant challenge for drug development (Genchi et al., 2022).

Other names

TMEM219Transmembrane protein 219IGFBP3RIGFBP-3-binding protein

IGFBP-3R mediates IGF-independent effects by binding to IGFBP-3, which induces the activation of caspase-8 and subsequent apoptosis, while also modulating TGF-beta and NF-kappaB signaling pathways.