Transforming growth factor beta receptor type 2 (TGFBR2) (TGFBR2)

Transforming growth factor beta receptor type 2 (TGFBR2) is a high-affinity transmembrane serine/threonine kinase receptor that binds the cytokine TGF-β, specifically the TGF-β1 and TGF-β3 isoforms (UniProt P37173). The extracellular domain (ECD) of TGFBR2 is the primary binding site for these ligands; upon binding, it forms a heterotetrameric complex with TGFBR1, leading to the phosphorylation of SMAD2 and SMAD3 proteins which then regulate the transcription of genes involved in cell proliferation, differentiation, and extracellular matrix production (Nature Reviews Molecular Cell Biology, 2012). In many advanced cancers, the TGF-β pathway is exploited to promote immune evasion by inhibiting T-cell activity and to drive metastasis through the induction of the epithelial-mesenchymal transition (EMT) (Nature Reviews Cancer, 2020). Therapeutic interventions often utilize the TGFBR2 ECD as a decoy or trap to sequester circulating TGF-β ligands, preventing them from activating cell-surface receptors and thereby reversing TGF-β-mediated immunosuppression and fibrosis (Journal of Hematology & Oncology, 2018). This approach is exemplified by bifunctional fusion proteins like Bintrafusp alfa, which targets both PD-L1 and TGF-β to enhance anti-tumor immunity (PubMed: 30333015). However, systemic inhibition of TGF-β via the TGFBR2 ECD is associated with specific safety concerns, including the development of benign skin tumors like keratoacanthomas and potential cardiovascular complications (Nature Reviews Drug Discovery, 2022).

Other names

TGF-beta receptor type IITGFR-2TGFbeta-RIITGF-beta trapTGFBR2-ECD

Ligand sequestration (decoy receptor) to inhibit TGF-β1 and TGF-β3 signaling pathways.