The type I transforming growth factor (TGF-)β receptor (TβRI or ALK-5) is an integral member of the TGF-β signaling pathway. TβRI consists of the extracellular domain, a single membrane-spanning domain and the intracellular domain. The extracellular domain facilitates ligand binding (TGF-β1, TGF-β2, TGF-β3 or IFG-BP3) and complex formation with the type II TGF-β receptor (TβRII) to initiate the canonical TGF-β cascade. As TβRI itself does not directly bind the TGF-β ligand, these receptor functions are displayed in the TβRII molecule page functions section. Upon assembly of the TβRII/TβRI complex, the intracellular domain of TβRI is phosphorylated by TβRII on a conserved GS domain, thus activating the kinase activity of TβRI. TβRI then phosphorylates the downstream effectors of the TGF-β signaling pathway, the Smad 2 and 3 transcription factors. TβRI is unable to directly bind TGF-β ligand, but forms a high-affinity heteromeric receptor complex with TβRII in the presence of ligand. After ligand binding and TβRI recruitment, the juxtamembrane GS domain of TβRI is phosphorylated by TβRII’s kinase activity, which activates the serine/threonine kinase activity of TβRI. Proteins that bind TβRI and inhibit or downregulate its activity include FKBP12, STRAP1, TRAP1, SMAD7 and SMURF1 and SMURF2.
Alternative names for this molecule:
ALK-5; ALK5 (human); R4 (rat); TbetaRI; TbRI; TGF-beta RI; TGF-beta type I receptor; Tgfbr1; TSR-1; Type I TGF-beta receptor