Transforming growth factor beta 1-Endoglin-TGF-beta receptor type II complex (TGF-β1/CD105/TβR-II)

The Endothelial TGF-β1/CD105/TβR-II receptor complex is a specialized signaling assembly primarily found on the surface of vascular endothelial cells that plays a central role in regulating angiogenesis and vascular homeostasis (UniProt P17813). It consists of the ligand Transforming Growth Factor-beta 1 (TGF-β1), the co-receptor Endoglin (CD105), and the signaling receptor TGF-beta receptor type II (TβR-II) (PMID: 10449775). Within this complex, Endoglin acts as a crucial modulator that facilitates the binding of TGF-β1 to TβR-II, which then recruits and phosphorylates type I receptors to initiate downstream signaling (PMID: 22431804). Specifically, the presence of Endoglin promotes signaling through the ALK1/Smad1/5/8 pathway, which stimulates endothelial cell proliferation and migration, while potentially antagonizing the ALK5/Smad2/3 pathway that inhibits these processes (PMID: 17210620). In pathological conditions such as cancer, the complex is often upregulated to facilitate tumor-induced angiogenesis, making it a significant target for anti-angiogenic therapy (PMID: 21632457). Drugs like carotuximab (TRC105) are designed to bind the CD105 component of this complex to inhibit ligand binding and induce antibody-dependent cellular cytotoxicity against proliferating endothelium (ClinicalTrials.gov NCT01432704). Furthermore, mutations in the genes encoding components of this complex, particularly ENG (CD105), are the primary cause of Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), a disorder characterized by vascular malformations (PMID: 15172001).

Other names

Endoglin-TGF-beta receptor complexCD105/TβRII complexEndothelial TGF-beta signaling complexTGFB1/ENG/TGFBR2 complex

The primary mechanism involves the competitive inhibition of ligand binding to the Endoglin (CD105) co-receptor, which disrupts the pro-angiogenic ALK1/Smad1/5/8 signaling pathway, and the induction of antibody-dependent cellular cytotoxicity (ADCC) against activated endothelial cells.