Recombinant Human LAP (TGF-beta 1) Protein, CF

• Reactivity: Hu
• Applications: Bioactivity
• Format: Carrier-Free

Recombinant Human LAP (TGF-beta 1) Protein, CF Summary

• Details of Functionality: Measured by its ability to inhibit TGF-beta 1 activity on HT‑2 mouse T cells. Tsang, M. et al. (1995) Cytokine 7:389. The ED₅₀ for this effect is 50-300 ng/mL in the presence of 1 ng/mL of Recombinant Human TGF‑ beta 1 (Catalog # 240-B).
• Source: Spodoptera frugiperda, Sf 21 (baculovirus)-derived human LAP (TGF-beta 1) protein
  Leu30-Arg278 (Cys33Ser)
• Accession #: P01137.2
• N-terminal Sequence: Leu30
• Structure / Form: Disulfide-linked homodimer
• Protein/Peptide Type: Recombinant Proteins
• Gene: TGFB1
• Purity: >97%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Endotoxin Note: <0.10 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• Theoretical MW: 27 kDa (monomer).
  Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
• SDS-PAGE: 28-36 kDa, reducing & 60-70 kDa, non-reducing conditions (variably glycosylated)

Packaging, Storage & Formulations

• Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  • 12 months from date of receipt, -20 to -70 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution.
  • 3 months, -20 to -70 °C under sterile conditions after reconstitution.
• Buffer: Lyophilized from a 0.2 μm filtered solution in PBS.
• Purity: >97%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Reconstitution Instructions: Reconstitute at 100 μg/mL in sterile PBS.

Notes

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Alternate Names for Recombinant Human LAP (TGF-beta 1) Protein, CF

• CED
• DPD1
• LAP (TGFbeta 1)
• LAP (TGF-beta 1)
• LAP
• TGFB
• TGFB1
• TGFbeta
• transforming growth factor beta 1

Background

TGF-  beta 1 (transforming growth factor beta 1) and the closely related TGF-beta 2 and -beta 3 are members of the large TGF-beta  superfamily. TGF‑  beta proteins are highly pleiotropic cytokines that regulate processes such as immune function, proliferation and epithelial‑mesenchymal transition (1‑3). Human TGF-beta 1 cDNA encodes a 390 amino acid (aa) precursor that contains a 29 aa signal peptide and a 361 aa proprotein (4). A furin-like convertase processes the proprotein within the trans-Golgi to generate an N-terminal 249 aa latency-associated peptide (LAP) and a C-terminal 112 aa mature TGF-  beta 1 (4‑6). Disulfide-linked homodimers of LAP and TGF-beta 1 remain non-covalently associated after secretion, forming the small latent TGF-beta 1 complex (4‑8). Purified LAP is also capable of associating with active TGF-beta with high affinity, and can neutralize TGF-beta activity (9). 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 (5‑7). TGF-beta activation from latency is controlled both spatially and temporally, by multiple pathways that include actions of proteases such as plasmin and MMP9, and/or by thrombospondin 1 or selected integrins (5, 8). The LAP portion of human TGF-beta 1 shares 91%, 92%, 85%, 86% and 88% aa identity with porcine, canine, mouse, rat and equine TGF-beta 1 LAP, respectively, while mature human TGF-beta 1 portion shares 100% aa identity with porcine, canine and bovine TGF-beta 1, and 99% aa identity with mouse, rat and equine TGF-beta 1. Although different isoforms of TGF-beta are naturally associated with their own distinct LAPs, the TGF-beta 1 LAP is capable of complexing with, and inactivating, all other human TGF-beta isoforms and those of most other species (9). Mutations within the LAP are associated with Camurati-Engelmann disease, a rare sclerosing bone dysplasia characterized by inappropriate presence of active TGF-beta 1 (10).

1. Dunker, N. & K. Krieglstein (2000) Eur. J. Biochem. 267:6982.
2. Wahl, S.M. (2006) Immunol. Rev. 213:213.
3. Chang, H. et al. (2002) Endocr. Rev. 23:787.
4. Derynck, R. et al. (1985) Nature 316:701.
5. Dabovic, B. and D.B. Rifkin (2008) “TGF-beta Bioavailability” in The TGF-beta Family. Derynck, R. and K. Miyazono (eds): Cold Spring Harbor Laboratory Press, p. 179.
6. Brunner, A.M. et al. (1989) J. Biol. Chem. 264:13660.
7. Miyazono, K. et al. (1991) EMBO J. 10:1091.
8. Oklu, R. and R. Hesketh (2000) Biochem. J. 352:601.
9. Miller, D.M. et al. (1992) Mol. Endocrinol. 6:694.
10. Janssens, K. et al. (2003) J. Biol. Chem. 278:7718.

Publications for LAP (TGF-beta 1) (246-LP/CF)(24)

Publications using 246-LP/CF

• AK Haudenschi, BE Sherlock, X Zhou, CS Sheaff, JC Hu, JK Leach, L Marcu, KA Athanasiou Non-destructive, continuous monitoring of biochemical, mechanical, and structural maturation in engineered tissue Scientific Reports, 2022-09-28;12(1):16227. 2022-09-28 [PMID: 36171228] (cell culture media, Bovine)
• W Wu, XR Huang, Y You, L Xue, XJ Wang, X Meng, X Lin, J Shen, X Yu, HY Lan, H Chen Latent TGF-beta1 protects against diabetic kidney disease via Arkadia/Smad7 signaling International journal of biological sciences, 2021-08-19;17(13):3583-3594. 2021-08-19 [PMID: 34512167] (Bioassay, Mouse)
• M Zhou, J Niu, J Wang, H Gao, M Shahbaz, Z Niu, Z Li, X Zou, B Liang Integrin &amp;alphav&amp;beta8 serves as a Novel Marker of Poor Prognosis in Colon Carcinoma and Regulates Cell Invasiveness through the Activation of TGF-&amp;beta1 J Cancer, 2020-04-06;11(13):3803-3815. 2020-04-06 [PMID: 32328185] (Bioassay, Human)
• J Basta, L Robbins, L Stout, MJ Prinsen, DW Griggs, M Rauchman Pharmacologic inhibition of RGD-binding integrins ameliorates fibrosis and improves function following kidney injury Physiol Rep, 2020-04-01;8(7):e14329. 2020-04-01 [PMID: 32281744] (Bioassay, Human)
• DC Briggs, AWW Langford-S, HL Birchenoug, TA Jowitt, CM Kielty, JJ Enghild, C Baldock, CM Milner, AJ Day Inter-&amp;alpha-inhibitor heavy chain-1 has an integrin-like 3D structure mediating immune regulatory activities and matrix stabilization during ovulation J. Biol. Chem., 2020-03-06;0(0):. 2020-03-06 [PMID: 32144206] (Surface Plasmon Resonance)
• Lynne A Murray The TGF-? inhibitory activity of antibody 37E1B5 depends on its H-CDR2 glycan MAbs, 2016-11-11;0(0):0. 2016-11-11 [PMID: 27834568] (Bioassay, Mouse)
• PSG9 Stimulates Increase in FoxP3+ Regulatory T-Cells through the TGF-?1 Pathway PLoS ONE, 2016-07-07;11(7):e0158050. 2016-07-07 [PMID: 27389696] (Surface Plasmon Resonance, Human)
• MH Fan, Q Zhu, HH Li, HJ Ra, S Majumdar, DL Gulick, JA Jerome, DH Madsen, M Christofid, DW Speicher, WW Bachovchin, C Feghali-Bo, E Puré Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice J. Biol. Chem., 2015-12-09;291(15):8070-89. 2015-12-09 [PMID: 26663085] (Bioassay)
• Turner C, Badu-Nkansah K, Crowley D, van der Flier A, Hynes R alpha5 and alphav integrins cooperate to regulate vascular smooth muscle and neural crest functions in vivo. Development, 2015-02-15;142(4):797-808. 2015-02-15 [PMID: 25670798] (Bioassay, Mouse)
• Fedele C, Singh A, Zerlanko B, Iozzo R, Languino L The alphavbeta6 integrin is transferred intercellularly via exosomes. J Biol Chem, 2015-01-07;290(8):4545-51. 2015-01-07 [PMID: 25568317] (Bioassay, Human)
• Ballesteros A, Mentink-Kane M, Warren J, Kaplan G, Dveksler G Induction and activation of latent transforming growth factor-beta1 are carried out by two distinct domains of pregnancy-specific glycoprotein 1 (PSG1). J Biol Chem, 2014-12-29;290(7):4422-31. 2014-12-29 [PMID: 25548275] (Surface Plasmon Resonance, Human)
• Guha R, Das S, Ghosh J, Sundar S, Dujardin J, Roy S Antimony resistant Leishmania donovani but not sensitive ones drives greater frequency of potent T-regulatory cells upon interaction with human PBMCs: role of IL-10 and TGF-beta in early immune response. PLoS Negl Trop Dis, 2014-07-17;8(7):e2995. 2014-07-17 [PMID: 25032977] (Bioassay, Human)
• Dutta A, Li J, Lu H, Akech J, Pratap J, Wang T, Zerlanko B, FitzGerald T, Jiang Z, Birbe R, Wixted J, Violette S, Stein J, Stein G, Lian J, Languino L Integrin alphavbeta6 promotes an osteolytic program in cancer cells by upregulating MMP2. Cancer Res, 2014-01-02;74(5):1598-608. 2014-01-02 [PMID: 24385215] (Bioassay, Human)
• Mele V, Muraro M, Calabrese D, Pfaff D, Amatruda N, Amicarella F, Kvinlaug B, Bocelli-Tyndall C, Martin I, Resink T, Heberer M, Oertli D, Terracciano L, Spagnoli G, Iezzi G Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-beta. Int J Cancer, 2014-01-30;134(11):2583-94. 2014-01-30 [PMID: 24214914] (Bioassay, Human)
• Willet J, Pichitsiri W, Jenkinson S, Brain J, Wood K, Alhasan A, Spielhofer J, Robertson H, Ali S, Kirby J Kidney transplantation: analysis of the expression and T cell-mediated activation of latent TGF-beta. J Leukoc Biol, 2012-11-27;93(4):471-8. 2012-11-27 [PMID: 23192429] (Bioassay, Human)
• Yamazaki S, Ema H, Karlsson G, Yamaguchi T, Miyoshi H, Shioda S, Taketo MM, Karlsson S, Iwama A, Nakauchi H Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell, 2011-11-23;147(5):1146-58. 2011-11-23 [PMID: 22118468] (In Vivo, Mouse)
• Oida T, Weiner HL Overexpression of TGF-ß 1 gene induces cell surface localized glucose-regulated protein 78-associated latency-associated peptide/TGF-ß. J. Immunol., 2010-08-18;185(6):3529-35. 2010-08-18 [PMID: 20720212] (Antibody Production, Mouse)
• Tran DQ, Glass DD, Uzel G, Darnell DA, Spalding C, Holland SM, Shevach EM Analysis of adhesion molecules, target cells, and role of IL-2 in human FOXP3+ regulatory T cell suppressor function. J. Immunol., 2009-03-01;182(5):2929-38. 2009-03-01 [PMID: 19234188] (Bioassay, Mouse)
• Savage ND, De Boer T, Walburg KV, Joosten SA, van Meijgaarden K, Geluk A, Ottenhoff TH Human anti-inflammatory macrophages induce Foxp3+ GITR+ CD25+ regulatory T cells, which suppress via membrane-bound TGFbeta-1. J. Immunol., 2008-08-01;181(3):2220-6. 2008-08-01 [PMID: 18641362] (Bioassay, Human)
• Rojas A, Meherem S, Kim YH, Washington MK, Willis JE, Markowitz SD, Grady WM The aberrant methylation of TSP1 suppresses TGF-beta1 activation in colorectal cancer. Int. J. Cancer, 2008-07-01;123(1):14-21. 2008-07-01 [PMID: 18425817] (Bioassay, Porcine)
• Van Aarsen LA, Leone DR, Ho S, Dolinski BM, McCoon PE, LePage DJ, Kelly R, Heaney G, Rayhorn P, Reid C, Simon KJ, Horan GS, Tao N, Gardner HA, Skelly MM, Gown AM, Thomas GJ, Weinreb PH, Fawell SE, Violette SM Antibody-mediated blockade of integrin alpha v beta 6 inhibits tumor progression in vivo by a transforming growth factor-beta-regulated mechanism. Cancer Res., 2008-01-15;68(2):561-70. 2008-01-15 [PMID: 18199553] (Bioassay, Human)
• Godfrey WR, Spoden DJ, Ge YG, Baker SR, Liu B, Levine BL, June CH, Blazar BR, Porter SB Cord blood CD4(+)CD25(+)-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function. Blood, 2004-09-16;105(2):750-8. 2004-09-16 [PMID: 15374887] (Bioassay, Human)
• Kitani A, Fuss I, Pedersen A, Nawata H TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J. Immunol., 2004-01-15;172(2):834-42. 2004-01-15 [PMID: 14707053] (Bioassay, Mouse)
• Zhang Y, McCormick LL, Gilliam AC Latency-associated peptide prevents skin fibrosis in murine sclerodermatous graft-versus-host disease, a model for human scleroderma. J. Invest. Dermatol., 2003-10-01;121(4):713-9. 2003-10-01 [PMID: 14632186] (In Vivo, Mouse)

Bioinformatics

• Gene Symbol: TGFB1
• Uniprot:
  • P01137.2()