TGF-beta1, Human, HEK293 Cells,Tag Free

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).

1.Derynck, R. and K. Miyazono (2008) Cold Spring Harbor Laboratory Press p. 29. 

2.Dunker, N. and K. Krieglstein (2000) Eur. J. Biochem. 267:6982. 

3.Wahl, S.M. (2006) Immunol. Rev. 213:213. 

4.Chang, H. et al. (2002) Endocr. Rev. 23:787. 

5.Lin, J.S. et al. (2006) Reproduction 132:179.

6.Hinck, A.P. et al. (1996) Biochemistry 35:8517. 

7.Mittl, P.R.E. et al. (1996) Protein Sci. 5:1261. 

8.Derynck, R. et al. (1985) Nature 316:701. 

9.Miyazono, K. et al. (1988) J. Biol. Chem. 263:6407. 

10.Oklu, R. and R. Hesketh (2000) Biochem. J. 352:601. 

11.de Caestecker, M. et al. (2004) Cytokine Growth Factor Rev. 15:1.