Recombinant Human GDF-15, Animal-Free Protein

GDF15 signals through GRAL and co-receptor RET leading to RET phosphorylation and signaling through the ERK and AKT pathway (reviewed in Emmerson et al., 2018). Bioactivity is determined using a luciferase reporter assay in HEK293T cells. Cells are treated (in triplicate) with a serial dilution of GDF15 or Qk010 TGF beta 1 for 6 hours. Firefly luciferase activity is measured and normalized to the control Renilla luciferase activity.

GDF15 migrates as a single band at 24 kDa in non-reducing (NR) and 13 kDa as a single monomeric species upon reduction (R). No contaminating protein bands are visible.Purified recombinant protein (7 µg) was resolved using 15% w/v SDS-PAGE in reduced (+ beta -mercaptothanol, R) and non-reduced conditions (NR) and stained with Coomassie Brilliant Blue R250.

• Reactivity: Hu
• Format: Carrier-Free

Recombinant Human GDF-15, Animal-Free Protein Summary

• Source: E. coli-derived human GDF-15 protein
• Accession #: Q99988.3
• Protein/Peptide Type: Animal-Free Recombinant Proteins
• Purity: Single species with expected mass
• Endotoxin Note: <0.10 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Theoretical MW: 25 kDa (dimer).
  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: Dimeric GDF-15 protein only

Packaging, Storage & Formulations

• Storage: Store lyophilized protein between -20 and -80 °C until the date of expiry. Avoid freeze-thaw cycles.
• Buffer: Lyophilized from acetonitrile/TFA
• Purity: Single species with expected mass
• Reconstitution Instructions: Resuspend in 10 mM HCl at >100 µg/ml, prepare single use aliquots, add carrier protein if desired

Notes

The above product was manufactured, tested and released by R&D System's contract manufacturer, Qkine Ltd, at 1 Murdoch House, Cambridge, UK, CB5 8HW. The product is for research use only and not for the diagnostic or theraputic use.

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

Alternate Names for Recombinant Human GDF-15, Animal-Free Protein

• GDF15
• GDF-15
• growth differentiation factor 15
• growth/differentiation factor 15
• Macrophage inhibitory cytokine 1
• MIC-1
• MIC-1NSAID-activated gene 1 protein
• MIC1Prostate differentiation factor
• NAG-1
• NAG-1NSAID-regulated gene 1 protein
• NSAID (nonsteroidal inflammatory drug)-activated protein 1
• PDF
• PDFGDF-15
• PLAB
• PLABNRG-1
• Placental bone morphogenetic protein
• Placental TGF-beta
• PTGF-beta
• PTGFBPTGF-beta

Background

Growth Differentiation Factor 15 (GDF-15), also called Macrophage Inhibitory Cytokine 1 (MIC-1), Placental Transforming Growth Factor beta , Prostate-derived Factor, and Placental Bone Morphogenetic Protein, is a divergent member of the TGF-beta superfamily (1, 2). Human GDF-15 shares 66% and 68% amino acid sequence identity with the rat and mouse proteins, respectively (3). GDF-15 is highly expressed in placenta and brain, and it is expressed at lower levels in kidney, pancreas, prostate, and colon. Similar to other TGF-beta family proteins, the GDF-15 proprotein is cleaved at a dibasic cleavage site (RxxR) to release the mature protein (4). The C-terminal domain of GDF-15 contains seven characteristic conserved cysteine residues necessary for the formation of the cysteine knot and the single interchain disulfide bond (5). Biologically active GDF-15 is a disulfide-linked homodimer of the mature protein and signals through the heterodimeric receptor composed of TGF-beta RI/ALK-5 and TGF-beta RII (6). GDF-15 has been shown to have various functions, including inhibition of TNF-alpha production from lipopolysaccharide-stimulated macrophages and the induction of cartilage formation (1, 5). GDF-15 also promotes neuronal survival, and hypothalamic expression of GDF-15 causes appetite suppression via modulation of Neuropeptide Y and Pro-opiomelanocortin levels (7-9). GDF-15 is cardioprotective via inhibition of platelet activation, limiting atherosclerosis, inhibiting CXCL1-induced neutrophil adhesion, regulating angiogenesis, and inhibiting norepinephrine-induced mycardial hypertrophy (6, 10-15).

1. Bootcov, M.R. et al. (1997) Proc. Natl. Acad. Sci. USA 94:11514.
2. Unsicker, K. et al. (2013) Cytokine Growth Factor Rev. 24:373.
3. Bottner, M. et al. (1999) Gene 237:105.
4. Fairlie, W.D. et al. (2001) J. Biol. Chem. 276:16911.
5. Paralkar, V.M. et al. (1998) J. Biol. Chem. 273:13760.
6. Artz, A. et al. (2016) Blood 128:529.
7. Johnen, H. et al. (2007) Nat. Med. 13:1333.
8. Strelau, J. et al. (2000) J. Neurosci. 20:8597.
9. Strelau, J. et al. (2009) J. Neurosci. 29:13640.
10. Whitson, R.J. et al. (2013) J. Cell. Biochem. 114:1424.
11. Rossaint, J. et al. (2013) J. Thromb. Haemost. 11:335.
12. Song, H. et al. (2012) Mol. Biol. Rep. 39:4017.
13. Preusch, M.R. et al. (2013) Eur. J. Med. Res. 18:19.
14. Kempf, T. et al. (2011) Nat. Med. 17:581.
15. Xu, X.-Y. et al. (2014) J. Biol. Chem. 289:10084.

Bioinformatics

• Uniprot:
  • Q99988.3()