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Recombinant human GDF-15 protein (Qk017)

Human growth differentiation factor 15 (GDF-15) protein is a member of the TGFβ family and subject of intense interest as a marker of cellular stress and for its role in metabolism, cancer and pregnancy.  Human GDF-15 also is functional in mouse studies.

Qkine GDF-15 is a 25 kDa disulfide-linked dimer composed of the mature domain of human GDF-15 protein. Our recombinant GDF-15 protein is exceptionally high purity, animal origin-free and extensively validated to ensure no trace contamination of related TGF-β family proteins from the mammalian culture systems.

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1000µg will be despatched as 2 x 500µg

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For any questions, please email orders@qkine.com

Summary

  • High purity human GDF-15 protein (Uniprot: Q99988)

  • >98%, by SDS-PAGE quantitative densitometry

  • 25 kDa (dimer). Mature active protein is a disulfide-linked dimer.

  • Expressed in E. coli

  • Animal origin-free (AOF)

  • Carrier protein-free

  • Manufactured in our Cambridge, UK laboratories

  • Lyophilized from acetonitrile, TFA

  • Resuspend in 10 mM HCl at >100 µg/ml (provided with protein and free of charge), prepare single use aliquots, add carrier protein if desired and store frozen at -20°C or -80°C

Featured applications

  • Biomarker for cellular stress

  • In vivo metabolic studies in mice (using human GDF-15)

Growth/differentiation factor 15, Macrophage inhibitory cytokine 1 (MIC 1), NSAID activated gene 1 protein (NAG1)

human

species similarity:
mouse – 67%
porcine – 67%
rat – 66%
bovine – 66%

Bioactivity

Human GDF15 Qk017 protein purity SDS-PAGE lot #011

GDF-15 signals through GRAL and co-receptor RET leading to RET phosphorylation and signalling through the ERK and AKT pathway (reviewed in Emmerson et al., 2018). Commercial sources of GDF-15, in particular those purified from mammalian expression systems, have been shown previously to be contaminated with trace amounts of TGF-β. These trace contaminants cause misleading experimental results due to the picomolar or even femtomolar EC50s (Olsen et al., 2017). Here we use a well-characterized SMAD2/3 activation assay to show that there is no contamination from other TGF-β family proteins. Bioactivity is determined using a luciferase reporter assay in HEK293T cells.  Cells are treated (in triplicate) with a serial dilution of GDF-15 or Qk010 TGF-β1 for 6 hours. Firefly luciferase activity is measured and normalized to the control Renilla luciferase activity. EC50 = 0 pM (no contamination with TGF-β or related growth factors). Data from Qk017 lot #104282

Purity

Human GDF15 Qk017 protein purity SDS-PAGE lot #011

GDF-15 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 (+β-mercaptothanol, R) and non-reduced conditions (NR) and stained with Coomassie Brilliant Blue R250.  Data from Qk017 lot #010

Further quality assays

  • Mass spectrometry: single species with expected mass

  • Analytical reversed-phase: single sharp peak

  • Endotoxin: <0.005 EU/μg protein (below level of detection)

  • Recovery from stock vial:  >95%

We are a company founded and run by scientists to provide a service and support innovation in stem cell biology and regenerative medicine.  All our products are exceptionally high purity, with complete characterisation and bioactivity analysis on every lot.

Protein background

Growth differentiation factor 15 (GDF-15) is a distant member of the TGF-β superfamily. Its expression is tightly regulated and circulating GDF-15 protein in serum is associated with diseases such as cancer, cardiovascular disease, obesity and metabolic disease. GDF-15 protein is being recognized as an important biomarker for cellular stress.

Unlike other members of the TGF-β superfamily that cause activation of the SMAD pathway, GDF-15 protein signals through GRAL and co-receptor RET leading to RET phosphorylation and signalling through the ERK and AKT pathway [1]. Commercial sources of recombinant human GDF-15 protein, in particular those purified from mammalian expression, are frequently contaminated with trace amounts of TGF-β and related proteins. These trace contaminants cause misleading experimental results due to the picomolar or even femtomolar EC50s of this family of cytokines [2].  Please be cautious with your source of recombinant GDF-15 protein, our scientists are happy to provide further information, please email support@qkine.com

We produce our proteins in E. coli with no animal products in our culture or purification processes to ensure there is no contamination from related proteins. In addition, we use a well-characterized SMAD2/3 activation assay to confirm there is no SMAD signalling.

[1] Emmerson, P. J., Duffin, K. L., Chintharlapalli, S. & Wu, X. GDF15 and Growth Control. Front. Physiol. 9, 1712 (2018). doi: 10.3389/fphys.2018.01712

[2] Olsen, O. E., Skjærvik, A., Størdal, B. F., Sundan, A. & Holien, T. TGF-β contamination of purified recombinant GDF15. PLoS One 12, e0187349 (2017). doi.org/10.1371/journal.pone.0187349

Publications using recombinant human GDF-15 protein (Qk017)

Activation of the hypothalamic–pituitary–adrenal axis by exogenous and endogenous GDF15
In PNAS on 29 June 2021 by Cimino, I. et al.

GDF15 linked to maternal risk of nausea and vomiting during pregnancy
In Nature on 13 December 2023 by Fejzo, M., Rocha, N., Cimino, I. et al.

Fetally-encoded GDF15 and maternal GDF15 sensitivity are major determinants of nausea and vomiting in human pregnancy
Preprint 4 June 2023 by Fejzo, M. et al.

The Common H202D Variant in GDF-15 Does Not Affect Its Bioactivity but Can Significantly Interfere with Measurement of Its Circulating Levels
In The Journal of Applied Laboratory Medicine November 2022 by Karusheva, Y. et al.

Our products are for research use only and not for diagnostic or therapeutic use.  Products are not for resale.

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