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

The Transforming growth factor beta receptor 2 (TGFBR2) is a transmembrane serine/threonine kinase receptor that forms a heterodimeric complex with TGFBR1 to bind TGF-beta ligands (TGFB1, TGFB2, TGFB3), initiating canonical SMAD-dependent signaling where TGFBR2 phosphorylates and activates TGFBR1, leading to SMAD2/3-SMAD4 complex formation and nuclear translocation for gene regulation. This pathway controls key processes including cell cycle arrest, epithelial and mesenchymal proliferation/differentiation, wound healing, extracellular matrix production, and immunosuppression. As a tumor suppressor, TGFBR2 mutations are linked to cancers, Marfan syndrome, Loeys-Dietz syndrome, and aortic aneurysms, often resulting in dysregulated signaling that promotes tumorigenesis or connective tissue defects. Structurally, it features an extracellular ligand-binding domain with a beta-sheet fold stabilized by disulfide bonds and a cytoplasmic kinase domain. Drug development targets TGFBR2 kinase inhibition to block pathological TGF-beta signaling in cancer and fibrosis, though challenges include selectivity over TGFBR1 and risks of promoting proliferation upon loss of suppression.

Other names

TGF-beta receptor type IITGF-beta receptor type-2TGFβ receptor IITGF-beta type II receptortbetaR-IITbetaRIITBR-IITGFR-2MFS2

Inhibition of kinase activity, Blocking TGF-beta binding, Disruption of receptor heterodimerization with TGFBR1, Prevention of SMAD phosphorylation