TGF-beta1, Human

TGF-beta1 (transforming growth factor beta 1) is one of three closely related mammalian members of the large TGF-beta1 superfamily that share a characteristic cystine knot structure. TGF-beta1, -2 and -3 are highly pleiotropic cytokines that act as cellular switches to regulate processes such as immune function, proliferation and epithelial-mesenchymal transition. Each TGF-beta isoform has some non-redundant function, for TGF-beta1, mice with targeted deletion show defects in hematopoiesis and endothelial differentiation and died of overwhelming inflammation. TGF-beta1 signaling begins with high-affinity binding to a type II ser/thr kinase receptor termed TGF-beta RII. This receptor then phosphorylates and activates a second ser/thr kinase receptor, TGF-beta RI (also called activin receptor-like kinase (ALK)-5), or alternatively, ALK-1. This complex phosphorylates and activates Smad proteins that regulate transcription.