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 (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). Recombinant protein corresponding to Ala279-Ser390 from human TGF-b1 expressed in HEK293 cells. Molecular Weight: ~12.8kD Biological Activity: Measured by its ability to inhibit the IL-4-dependent proliferation of HT-2 mouse T cells. Tsang, M. et al. (1995) Cytokine 7:389. The ED50 for this effect is 0.04-0.2ng/ml Storage and Stability: Lyophilized and reconstituted products are stable for 6 months after receipt at -20C. Reconstitute with sterile 4mM HCl. Aliquot to avoid repeated freezing and thawing. Store at -20C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
