Human LAP (TGF-beta 1) Antibody

TGF-  beta1 (transforming growth factor beta 1) and the closely related TGF-beta 2 and -beta 3 are members of the large TGF-beta  superfamily. TGF-  beta proteins are highly pleiotropic cytokines that regulate processes such as immune function, proliferation and epithelial-mesenchymal transition (1‑3). Human TGF-beta 1 cDNA encodes a 390 amino acid (aa) precursor that contains a 29 aa signal peptide and a 361 aa proprotein (4). A furin-like convertase processes the proprotein within the trans-Golgi to generate an N-terminal 249 aa (aa 30-278) latency-associated peptide (LAP) and a C-terminal 112 aa (aa 279-390) mature TGF-  beta1 (4‑6). Disulfide-linked homodimers of LAP and TGF-beta 1 remain non-covalently associated after secretion, forming the small latent TGF-beta 1 complex (4‑8). Purified LAP is also capable of associating with active TGF-beta with high affinity, and can neutralize TGF-beta activity (9). 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 (5‑7). TGF-beta activation from latency is controlled both spatially and temporally, by multiple pathways that include actions of proteases such as plasmin and MMP9, and/or by thrombospondin 1 or selected integrins (5, 8). The LAP portion of human TGF-beta 1 shares 91%, 92%, 85%, 86% and 88% aa identity with porcine, canine, mouse, rat and equine TGF-beta 1 LAP, respectively, while mature human TGF-beta 1 portion shares 100% aa identity with porcine, canine and bovine TGF-beta 1, and 99% aa identity with mouse, rat and equine TGF-beta 1. Although different isoforms of TGF-beta are naturally associated with their own distinct LAPs, the TGF-beta 1 LAP is capable of complexing with, and inactivating, all other human TGF-beta isoforms and those of most other species (9). Mutations within the LAP are associated with Camurati-Engelmann disease, a rare sclerosing bone dysplasia characterized by inappropriate presence of active TGF-beta 1 (10).