TGF- 1 (transforming growth factor beta 1) is one of three closely related mammalian members of the large TGF- 1 superfamily that share a characteristic cystine knot structure TGF- 1 -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- isoform has some non-redundant function for TGF- 1 mice with targeted deletion show defects in hematopoiesis and endothelial differentiation and died of overwhelming inflammation TGF- 1 signaling begins with high-affinity binding to a type II ser/thr kinase receptor termed TGF- RII This receptor then phosphorylates and activates a second ser/thr kinase receptor TGF- RI (also called activin receptor like kinase (ALK)-5) or alternatively ALK-1 This complex phosphorylates and activates Smad proteins that regulate transcription