Background

TGF-β1 (transforming growth factor beta 1) is one of three closely related mammalian members of the large TGF-β superfamily that share a characteristic cystine knot structure (1–7). TGF-β1, -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-β isoform has some non-redundant functions; for TGF-β1, mice with targeted deletion show defects in hematopoiesis and endothelial differentiation, and die of overwhelming inflammation (2).

Human TGF-β1 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-β1 (8, 9). Disulfide-linked homodimers of LAP and TGF-β1 remain non-covalently associated after secretion, forming the small latent TGF-β1 complex (8–10). Covalent linkage of LAP to one of three latent TGF-β binding proteins (LTBPs) creates a large latent complex that may interact with the extracellular matrix (9, 10). TGF-β is activated from latency by pathways that include the actions of protease plasmin, matrix metalloproteases, thrombospondin-1, and a subset of integrins (10).

Mature human TGF-β1 shares 100% aa identity with pig, dog, and cow TGF-β1, and 99% aa identity with mouse, rat, and horse TGF-β1. It demonstrates cross-species activity (1). TGF-β1 signaling begins with high-affinity binding to a type II ser/thr kinase receptor termed TGF-βRII. This receptor then phosphorylates and activates a second ser/thr kinase receptor, TGF-βRI (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-βRIII) and endoglin, or use of Smad-independent signaling pathways, allow for disparate actions observed in response to TGF-β in different contexts (11).

Reference

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.

12.Zuniga, J.E. et al. (2005) J. Mol. Biol. 354:1052.

Specifications

Synonyms	TGF-beta 1 protein; TGFbeta 1; TGF-beta 1; TGFbeta; TGF-beta-1; transforming growth factor beta-1; transforming growth factor, beta 1.
Accession #	P01137.
Source	HEK293
Source	Ala279-Ser390
Predicted Moleucular weight	12.8kDa(monomer) 25.6kDa(Dimer)

Components and Storage

Formulation	Solution protein
	Dissolved in sterile 20 mM sodium citrate(pH=2.5) buffer .
	This solution can be diluted into other aqueous buffers. Centrifuge the vial prior to opening.
Storage and Stability	Avoid repeated freeze-thaw cycles.
	It is recommended that the protein be aliquoted for optimal storage.
	12 months from date of receipt, -20 to -70 C as supplied.
Shipping	Shipping with dry ice.

Quality

Purity	> 95%, determined by SDS-PAGE.
Endotoxin Level	<0.010 EU per 1 ug of the protein by the LAL method.
Activity	Measured by the(CAGA)₁₂-luciferase reporter assay.
Activity	The EC50 for this effect is 25 ng/mL.

SDS-PAGE

Bioactivity

Documents

Human TGFb1