TGF-beta 1/1.2 Antibody

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 cystine knot structure. 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. 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. Human TGF-beta 1 cDNA encodes a 390 amino acid (aa) precursor that contains a 29 aa signal peptide and a 361 aa proprotein. 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- beta1. Disulfide-linked homodimers of LAP and TGF-beta 1 remain non-covalently associated after secretion, forming the small latent TGF-beta 1 complex. 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. TGF-beta is activated from latency by pathways that include actions of the protease plasmin, matrix metalloproteases, thrombospondin 1 and a subset of integrins. 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. 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. 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.