TGF-beta type II receptor

Transforming growth factor β (TGFβ) is a polypeptide cytokine that has a vital role in regulating cellular proliferation and differentiation, as well as tissue specific processes including angiogenesis and wound healing. The type II TGFβ receptor (TβRII) is a constitutively active cell surface serine/threonine kinase receptor. The TGFβ isoform homodimers either directly bind to TβRII or are presented to TβRII by the accessory type III TGFβ receptor (TβRIII, betaglycan). TβRII has affinity for TGF-β1 and TGF-β3 isoforms but requires TβRIII to bind TGF-β2. Upon ligand binding, TβRII forms a complex with TβR1 (ALK-5) and phosphorylates the juxtamembrane GS domain of TβRI to activate its serine/threonine kinase. In turn, the receptor activated transcription factors Smad 2 and Smad 3 are phosphorylated by TβRI. Phosphorylated Smad2/Smad3 then bind Smad4 and translocate to the nucleus to enable interaction with other transcription factors and regulate the transcription of TGFβ responsive genes. In endothelial cells, upon ligand binding, TβRII can also form a complex with and activate ALK-1, which then phosphorylates Smads (Smads 1/5/8) to mediate a distinct signaling pathway.