TGF-beta 3 Antibody

TGF-beta 3 (transforming growth factor beta 3) is one of three closely related mammalian members of the large TGF-beta superfamily that share a characteristic cystine 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 3, mice with targeted deletion show defects palatogenesis and pulmonary development (2). Human TGF-beta 3 cDNA encodes a 412 amino acid (aa) precursor that contains a 20 aa signal peptide and a 392 aa proprotein (8). A furin-like convertase processes the proprotein to generate an N-terminal 220 aa latency-associated peptide (LAP) and a C-terminal 112 aa mature TGF-beta 3 (8, 9). Disulfide-linked homodimers of LAP and TGF-beta 3 remain non-covalently associated after secretion, forming the small latent TGF-beta 3 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 3 shows 100%, 99% and 98% aa identity with mouse/dog/horse, rat and pig TGF-beta 3, respectively. It demonstrates cross-species activity (1). TGF-beta 3 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).