Transforming growth factor beta receptor type I or type II (TGFBRI (also known as ALK5), TGFBRII)

The transforming growth factor beta receptor type I and type II are single-pass transmembrane serine/threonine kinase receptors that mediate signaling of the transforming growth factor beta (TGF-β) superfamily[3][5]. Upon ligand binding, the type II receptor (TGFBRII) recruits and phosphorylates the type I receptor (TGFBRI/ALK5), which in turn phosphorylates receptor-regulated SMAD proteins (SMAD2/3), ultimately regulating gene transcription in the nucleus[1][2][3][5]. These receptors regulate diverse cellular processes including cell growth, differentiation, apoptosis, immune modulation, wound healing, and fibrosis[2][4][5]. Dysregulation of TGF-β signaling via these receptors is implicated in cancers, fibrotic diseases, inflammation, and immune disorders[3][5]. TGF-β pathway inhibitors, including kinase inhibitors (galunisertib, vactosertib), ligand-neutralizing antibodies (fresolimumab), and ligand/receptor traps (bintrafusp alfa), are in development or clinical use for various diseases. Safety concerns include immunosuppression, impaired healing, and pro-tumorigenic effects in some disease stages[5][7]. The target as stated, “Transforming growth factor beta receptor I/II pathway,” combines two distinct receptor proteins and a signaling pathway. The proper targets are the individual receptors—“Transforming growth factor beta receptor type I (TGFBRI/ALK5)” and “Transforming growth factor beta receptor type II (TGFBRII)”—each of which is a drug target[3][5][8]. The “pathway” term is not a canonical molecular target; thus, the entry as given is not a precise or correct target name and “is_incorrect” should be set to true.

Other names

Activin receptor-like kinase 5 (ALK5) (for type I)TβRITβRIITGF-beta receptor type I/IITGF-β receptor I/II

Small-molecule inhibitor of kinase activity, Antibody neutralizing TGF-β ligand, Ligand trap/fusion protein, Inhibition of receptor dimerization