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‑ beta1 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‑ beta1 (8, 9). Disulfide‑linked homodimers of LAP and TGF‑ beta1 remain non‑covalently associated after secretion, forming the small latent TGF‑ beta1 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‑ beta1 shares 100% aa identity with pig, dog and cow TGF‑ beta1, and 99% aa identity with mouse, rat and horse TGF‑ beta1. It demonstrates cross‑species activity (1). TGF‑ beta1 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 known as Activin Receptor‑Like Kinase 5(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).

References

Derynck, R. and K. Miyazono (2008) Cold Spring Harbor Laboratory Press, 29.
Dunker, N. and K. Krieglstein (2000) Eur. J. Biochem. 267:6982.
Wahl, S.M. (2006) Immunol. Rev. 213:213.
Chang, H. et al. (2002) Endocr. Rev. 23:787.
Lin, J.S. et al. (2006) Reproduction 132:179.
Hinck, A.P. et al. (1996) Biochemistry 35:8517.
Mittl, P.R.E. et al. (1996) Protein Sci. 5:1261.
Derynck, R. et al. (1985) Nature 316:701.
Miyazono, K. et al. (1988) J. Biol. Chem. 263:6407.
Oklu, R. and R. Hesketh (2000) Biochem. J. 352:601.
de Caestecker, M. et al. (2004) Cytokine Growth Factor Rev. 15:1.
Zuniga, J.E. et al. (2005) J. Mol. Biol. 354:1052.

Long Name

Latency-associated Peptide

Alternate Names

LAP (TGFbeta 1)

Entrez Gene IDs

7040 (Human)

Gene Symbol

TGFB1

UniProt

P04202

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This product is provided under an intellectual property license from Life Technologies Corporation. The transfer of this product is conditioned on the buyer using the purchased product solely in research conducted by the buyer, excluding contract research or any fee for service research, and the buyer must not (1) use this product or its components for (a) diagnostic, therapeutic or prophylactic purposes; (b) testing, analysis or screening services, or information in return for compensation on a per-test basis; or (c) manufacturing or quality assurance or quality control, and/or (2) sell or transfer this product or its components for resale, whether or not resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5781 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@thermofisher.com.

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Mouse LAP (TGF-beta 1) Alexa Fluor™ Plus 488-conjugated Antibody

R&D Systems, part of Bio-Techne | Catalog # FAB7666AFP488

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Background: LAP (TGF-beta 1)