Recombinant Human Gremlin Protein, CF Summary
Product Specifications
Lys25-Asp184, with a C-terminal 10-His tag
Analysis
Product Datasheets
Carrier Free
CF stands for Carrier Free (CF). We typically add Bovine Serum Albumin (BSA) as a carrier protein to our recombinant proteins. Adding a carrier protein enhances protein stability, increases shelf-life, and allows the recombinant protein to be stored at a more dilute concentration. The carrier free version does not contain BSA.
In general, we advise purchasing the recombinant protein with BSA for use in cell or tissue culture, or as an ELISA standard. In contrast, the carrier free protein is recommended for applications, in which the presence of BSA could interfere.
5190-GR
Formulation | Lyophilized from a 0.2 μm filtered solution in PBS and EDTA. |
Reconstitution | Reconstitute at 200 μg/mL in sterile PBS. |
Shipping | The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below. |
Stability & Storage: | Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
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Scientific Data
Recombinant Human Gremlin (Catalog # 5190-GR) inhibits BMP-4-induced alkaline phosphatase production in the MC3T3-E1 mouse preosteoblast cell line. The ED50 for this effect is 0.025-0.15 µg/mL in the presence of 30 ng/mL of Recombinant Human BMP-4 (Catalog # 314-BP).
1 µg/lane of Recombinant Human Gremlin was resolved with SDS-PAGE under reducing (R) conditions and visualized by silver staining, showing major bands at 25‑30 kDa. Multiple bands in gel are due to variable glycosylation.
Reconstitution Calculator
Background: Gremlin
Gremlin, also known as Increased in High Glucose protein 2 (IHG-2) and Down-regulated in Mos-transformed cells protein (Drm), is a 28 kDa member of the Dan family of secreted glycoproteins (1-3). Human Gremlin is synthesized as a 184 amino acid (aa) precursor that contains a 24 aa signal sequence and a 160 aa mature region (SwissProt # O60565). The mature region contains one potential site for N-linked glycosylation (Asn 42), a cysteine-rich region, and a cysteine-knot motif (aa 94‑184) whose structure is shared by members of the TGF-beta superfamily (3). Post-translational modifications include glycosylation and phosphorylation (3). Gremlin exists in both secreted and membrane-associated forms (3). There are two isoforms for human Gremlin. Isoform 1 is the standard protein, and in isoform 2, there is a deletion of aa 39‑79. Human Gremlin shares 99% and 86% aa sequence identity with mouse and chick Gremlin, respectively. Northern blot analysis shows that Gremlin mRNA is highly expressed in the small intestine, fetal brain and colon, and weakly expressed in adult brain, ovary, prostate, pancreas and skeletal muscle (4). Gremlin functions as a bone morphogenetic protein (BMP) antagonist. It acts by binding to, and forming heterodimers with, BMP-2, BMP-4, and BMP-7, thus preventing them from interacting with their cell surface receptors (1). This mechanism is thought to be responsible for the pattern-inducing activity of Gremlin during embryonic development (5) and to play a role in human diseases, such as diabetic nephropathy (6). However, intracellular BMP-independent mechanisms of action (7) may mediate the ability of Gremlin to suppress transformation and tumorigenesis under certain experimental conditions (8-9). Gremlin also interacts with Slit proteins and acts as an inhibitor of monocyte chemotaxis (10). In addition, Gremlin has been found to be a proangiogenic factor expressed by endothelium (9).
- Hsu, D.R. et al. (1998) Mol. Cell 1:673.
- McMahon, R. et al. (2000) J. Biol. Chem. 275:9901.
- Wordinger, R.J. et al. (2008) Exp. Eye Res. 87:78.
- Topol, L.Z. et al. (2000) Cytogenet. Cell Genet. 89:79.
- Khokha, M.K. et al. (2003) Nat. Genet. 34:303.
- Lappin, D.W. et al. (2002) Nephrol. Dial. Transplant 17:65.
- Chen, B. et al. (2002) Biochem. Biophys. Res. Commun. 295:1135.
- Topol, L.Z. et al. (1997) Mol. Cell. Biol. 17:4801.
- Stabile, H. et al. (2007) Blood 109:1834.
- Chen, B. et al. (2004) J. Immunol. 173:5914.
Citations for Recombinant Human Gremlin Protein, CF
R&D Systems personnel manually curate a database that contains references using R&D Systems products. The data collected includes not only links to publications in PubMed, but also provides information about sample types, species, and experimental conditions.
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Citations: Showing 1 - 10
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alphaVbeta8 integrin targeting to prevent posterior capsular opacification (PCO)
Authors: MH Shihan, SG Novo, Y Wang, D Sheppard, A Atakilit, TD Arnold, NM Rossi, AP Faranda, MK Duncan
JCI Insight, 2021-11-08;0(0):.
Species: Mouse
Sample Types: In Vivo
Applications: In Vivo -
Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway
Authors: NJ Sung, NH Kim, YJ Surh, SA Park
International Journal of Molecular Sciences, 2020-12-03;21(23):.
Species: Human
Sample Types: Whole Cells
Applications: Cell Culture -
Gremlin-1 augments the oestrogen-related receptor alpha signalling through EGFR activation: implications for the progression of breast cancer
Authors: SA Park, NJ Sung, BJ Choi, W Kim, SH Kim, YJ Surh
Br. J. Cancer, 2020-06-23;0(0):.
Species: Human
Sample Types: Spheroid
Applications: Cell Culture -
DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells
Authors: NJ Sung, NH Kim, NY Bae, HS Jo, SA Park
Biosci. Rep., 2020-03-27;40(3):.
Species: Human
Sample Types: Whole Cells
Applications: Cell Culture -
ECHO, the executable CHOndrocyte: A computational model to study articular chondrocytes in healthy and disease
Authors: S Schivo, S Khurana, K Govindaraj, J Scholma, J Kerkhofs, L Zhong, X Huang, J van de Pol, R Langerak, AJ van Wijnen, L Geris, M Karperien, JN Post
Cell. Signal., 2019-12-11;0(0):109471.
Species: Human
Sample Types: Whole Cells
Applications: Bioassay -
No evidence of Gremlin1-mediated activation of VEGFR2 signalling in endothelial cells
Authors: LR Dutton, CL O' Neill, RJ Medina, DP Brazil
J. Biol. Chem., 2019-10-11;0(0):.
Species: Human
Sample Types: Whole Cells
Applications: Cell Culture -
Targeting chemoresistant colorectal cancer via systemic administration of a BMP7 variant
Authors: V Veschi, LR Mangiapane, A Nicotra, S Di Franco, E Scavo, T Apuzzo, DS Sardina, M Fiori, A Benfante, ML Colorito, G Cocorullo, F Giuliante, C Cipolla, G Pistone, MR Bongiorno, A Rizzo, CM Tate, X Wu, S Rowlinson, LF Stancato, M Todaro, R De Maria, G Stassi
Oncogene, 2019-10-07;0(0):.
Species: Human
Sample Types: Whole Cells
Applications: Bioassay -
Cancer-associated fibroblast-derived Gremlin 1 promotes breast cancer progression
Authors: J Ren, M Smid, J Iaria, DCF Salvatori, H van Dam, HJ Zhu, JWM Martens, P Ten Dijke
Breast Cancer Res., 2019-09-18;21(1):109.
Species: Human
Sample Types: Whole Cells
Applications: Bioassay -
Organoid culture media formulated with growth factors of defined cellular activity
Authors: M Urbischek, H Rannikmae, T Foets, K Ravn, M Hyvönen, M de la Roch
Sci Rep, 2019-04-17;9(1):6193.
Species: Human, Mouse
Sample Types: Whole Cells
Applications: Bioassay -
Generation and Applications of a DNA Aptamer against Gremlin-1
Authors: Q Li, Y Huo, Y Guo, X Zheng, W Sun, Z Hao
Molecules, 2017-04-28;22(5):.
Applications: Bioassay -
Diverse feather shape evolution enabled by coupling anisotropic signalling modules with self-organizing branching programme
Authors: A Li, S Figueroa, TX Jiang, P Wu, R Widelitz, Q Nie, CM Chuong
Nat Commun, 2017-01-20;8(0):ncomms14139.
Species: Chicken
Sample Types: In Vivo
Applications: In Vivo -
Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin.
Authors: Olsen O, Wader K, Misund K, Vatsveen T, Ro T, Mylin A, Turesson I, Stordal B, Moen S, Standal T, Waage A, Sundan A, Holien T
Blood Cancer J, 2014-03-21;4(0):e196.
Species: Human
Sample Types: Whole Cells
Applications: Bioassay -
Interleukin-6 (IL-6) trans signaling drives a STAT3-dependent pathway that leads to hyperactive transforming growth factor-beta (TGF-beta) signaling promoting SMAD3 activation and fibrosis via Gremlin protein.
Authors: O'Reilly S, Ciechomska M, Cant R, van Laar J
J Biol Chem, 2014-02-18;289(14):9952-60.
Species: Human
Sample Types: Whole Cells
Applications: Bioassay -
Quantitative kinetics analysis of BMP2 uptake into cells and its modulation by BMP antagonists.
Authors: Alborzinia H, Schmidt-Glenewinkel H, Ilkavets I, Breitkopf-Heinlein K, Cheng X, Hortschansky P, Dooley S, Wolfl S
J Cell Sci, 2012-10-17;126(0):117-27.
Species: Human
Sample Types: Whole Cells
Applications: Bioassay -
Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors.
Authors: Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, Ribas A, Li J, Moffat J, Sutherlin DP, Koeppen H, Merchant M, Neve R, Settleman J
Nature, 2012-07-26;487(7408):505-9.
Species: Human
Sample Types: Whole Cells
Applications: Bioassay -
Gremlin-1 induces BMP-independent tumor cell proliferation, migration, and invasion.
Authors: Kim M, Yoon S, Lee S
PLoS ONE, 2012-04-13;7(4):e35100.
Species: Human
Sample Types: Whole Cells
Applications: Flow Cytometry -
Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2.
Authors: Mitola S, Ravelli C, Moroni E, Salvi V, Leali D, Ballmer-Hofer K, Zammataro L, Presta M
Blood, 2010-07-21;116(18):3677-80.
Species: Human
Sample Types: Recombinant Protein
Applications: Surface Plasmon Resonance
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