R&D Systems Human TGF-beta 1 Protein, CF (10 UG) Item ID: RDS100B010CF

TGF-beta 1 (transforming growth factor beta 1) is one of three closely related mammalian members of the large TGF-beta  superfamily that share a characteristic cysteine knot structure (1-7). TGF-beta 1, -2 and -3 are highly pleiotropic cytokines that are proposed to act as cellular switches that regulate processes such as immune function, proliferation and epithelial-mesenchymal transition (1-4). Each TGF-beta isoform has some non-redundant functions; for TGF-beta 1, mice with targeted deletion show defects in hematopoiesis and endothelial differentiation, and die of overwhelming inflammation (2). Human TGF-beta 1 cDNA encodes a 390 amino acid (aa) precursor that contains a 29 aa signal peptide and a 361 aa proprotein (8). A furin-like convertase processes the proprotein to generate an N-terminal 249 aa latency-associated peptide (LAP) and a C-terminal 112 aa mature TGF-  beta 1 (8, 9). Disulfide-linked homodimers of LAP and TGF-beta 1 remain non-covalently associated after secretion, forming the small latent TGF-beta 1 complex (8-10). Covalent linkage of LAP to one of three latent TGF-beta binding proteins (LTBPs) creates a large latent complex that may interact with the extracellular matrix (9, 10). TGF-beta is activated from latency by pathways that include actions of the protease plasmin, matrix metalloproteases, thrombospondin 1 and a subset of integrins (10). Mature human TGF-beta 1 shares 100% aa identity with pig, dog and cow TGF-beta 1, and 99% aa identity with mouse, rat and horse TGF-beta 1. It demonstrates cross-species activity (1). TGF-beta 1 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 (3, 11, 12). Contributions of the accessory receptors betaglycan (also known as TGF-beta  RIII) and endoglin, or use of Smad-independent signaling pathways, allow for disparate actions observed in response to TGF-beta in different contexts (11).