Transforming growth factor beta receptor (TGFBR) (TGFBR)

The Transforming growth factor beta (TGF-beta) receptor complex is a transmembrane signaling unit composed of Type I (TGFBR1) and Type II (TGFBR2) serine/threonine kinase subunits (UniProt: P36897, P37173). Upon binding of TGF-beta ligands, the Type II receptor phosphorylates and activates the Type I receptor, which subsequently triggers the canonical SMAD signaling pathway or non-canonical pathways like MAPK to regulate gene transcription (StatPearls: TGF-beta Signaling). This signaling axis plays a dual role in human physiology; it acts as a potent tumor suppressor in normal epithelium but transitions into a promoter of epithelial-mesenchymal transition (EMT), metastasis, and immunosuppression in advanced malignancies (PMID: 28944402). Beyond oncology, dysregulated TGF-beta signaling is a primary driver of tissue fibrosis in the lungs, liver, and kidneys, as well as various cardiovascular pathologies like Marfan syndrome. Pharmacological intervention typically involves small molecule inhibitors targeting the TGFBR1 kinase domain or monoclonal antibodies and "traps" that sequester the ligands to prevent receptor engagement (PMID: 30635930).

Other names

TGF-beta receptorTGFBR1TGFBR2ALK5TbetaR-ITbetaR-IISerine/threonine-protein kinase receptor type 1

Inhibition of the serine/threonine kinase activity of the Type I receptor (TGFBR1/ALK5) or neutralization of TGF-beta ligands to prevent receptor activation and downstream SMAD signaling (PMID: 30635930).