Recombinant Human LIF Protein

• Reactivity: Hu
• Applications: Bioactivity

Recombinant Human LIF Protein Summary

• Details of Functionality: Measured in a cell proliferation assay using TF‑1 human erythroleukemic cells. Kitamura, T. et al. (1989) J. Cell Physiol. 140:323. The ED₅₀ for this effect is 0.02-0.12 ng/mL.
• Source: E. coli-derived human LIF protein
  Pro24-Phe202
• Accession #: P15018
• N-terminal Sequence: Pro24
• Protein/Peptide Type: Recombinant Proteins
• Gene: LIF
• Purity: >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Endotoxin Note: <0.01 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• Theoretical MW: 19.6 kDa.
  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: 19 kDa, reducing conditions

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 with BSA as a carrier protein.
• Purity: >95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Reconstitution Instructions: Reconstitute at 100 μg/mL in PBS containing at least 0.1% human or bovine serum albumin.

Notes

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

Alternate Names for Recombinant Human LIF Protein

• CDF
• D Factor
• DIA
• differentiation inhibitory activity
• differentiation stimulating factor
• Differentiation-stimulating factor
• Emfilermin
• HILDA
• HILDAcholinergic differentiation factor
• leukemia inhibitory factor (cholinergic differentiation factor)
• leukemia inhibitory factor
• LIF
• Melanoma-derived LPL inhibitor
• MLPLI

Background

LIF (leukemia inhibitory factor) is a widely expressed, highly and variably glycosylated, 32‑62 kDa, monomeric, pleiotropic cytokine in the IL‑6 family of helical cytokines (1‑4). The first exon encoding the signal sequence is alternately spliced, resulting in LIF-D, LIF-M, and LIF‑T mRNAs that produce secreted, extracellular matrix‑associated, and intracellular forms, respectively (5). LIF-D and LIF-M mRNAs produce identical 180 amino acid (aa) mature sequences (5). Mature human LIF (180 aa) shares 78%, 82%, 91%, 88 and 87% aa sequence identity with mouse, rat, canine, bovine, and porcine LIF, respectively. The LIF receptor is a heterodimer of a type I transmembrane ligand‑binding subunit, LIFR (gp190), and the type I transmembrane signal transducing subunit, gp130, signaling especially through STAT3 and JAK kinases (3, 4, 6). Gp130 and members of the LIFR family also mediate the biological effects of Oncostatin M, Cardiotrophin‑1, Galectin‑10, CNTF, IL‑6,
IL‑11, and IL‑27 (3, 6). A soluble LIFR has been reported in the mouse (7). Depending on the cells and their context, LIF either opposes or favors differentiation (3, 8). LIF produced by the uterine endometrium supports successful implantation of the embryo, promotes proliferation and maintenance of pluripotency in embryonic stem cells, and favors proliferation of progenitor cell types such as hematopoietic stem cells (3, 6, 8). However, excess LIF blocks differentiation of embryoid bodies, indicating the importance of LIF regulation (3, 6). LIF is produced by CD4⁺ T cells in response to activation, and is required by the thymic epithelium to support T cell maturation (3, 4). LIF expression is up‑regulated by neuronal injury, and promotes motor neuron survival and oligodendrocyte myelination (3, 4, 9). LIF is produced by the adrenal cortex and likely enhances its production of cortisol and aldosterone (10). LIF can function as an autocrine growth factor in some pancreatic cancers, but induces differentiation in the myeloid leukemic cell line M1 (2, 11). Tumor LIF can also induce formation of immunosuppressive tumor‑associated macrophages (12). LIF promotes endometrial remodeling and differentiation of adipocytes and cardiac smooth muscle cells (3, 4). It promotes regulatory T cell and inhibits Th17 cell differentiation, thus promoting tolerance, down‑regulating inflammation, and contributing to immune tolerance during pregnancy and in the nervous system (3, 4, 6, 8).

1. Gough, N.M. et al. (1988) Proc. Natl. Acad. Sci. USA 85:2623.
2. Moreau, J.F. et al. (1988) Nature 336:690.
3. Trouillas, M. et al. (2009) Eur. Cytokine Netw. 20:51.
4. Metcalfe, S.M. (2011) Genes Immun. 12:157.
5. Voyle, R.B. et al. (1999) Exp. Cell Res. 249:199.
6. Cheng, J.G. et al. (2001) Proc. Natl. Acad. Sci. USA 98:8680.
7. Tomida, M. et al. (1993) FEBS lett. 334:193.
8. Paiva, P. et al. (2009) Cytokine Growth Factor Rev. 20:319.
9. Slaets, H. et al. (2010) Trends Mol. Med. 16:493.
10. Bamberger, A.M. et al. (2000) Mol. Cell. Endocrinol. 162:145.
11. Kamohara, H. et al. (2007) Int. J. Oncol. 30:977.
12. Duluc, D. et al. (2007) Blood 110:4319.

Publications for LIF (7734-LF)(28)

Publications using 7734-LF

• Jovanovic, VM;Weber, C;Slamecka, J;Ryu, S;Chu, PH;Sen, C;Inman, J;De Sousa, JF;Barnaeva, E;Hirst, M;Galbraith, D;Ormanoglu, P;Jethmalani, Y;Mercado, JC;Michael, S;Ward, ME;Simeonov, A;Voss, TC;Tristan, CA;Singeç, I; A defined roadmap of radial glia and astrocyte differentiation from human pluripotent stem cells Stem cell reports 2023-07-04 [PMID: 37451260] (Bioassay, Human)
• J Li, Q Zhu, J Cao, Y Liu, Y Lu, Y Sun, Q Li, Y Huang, S Shang, X Bian, C Li, L Zhang, Y Wang, Y Nie, J Fu, W Li, MA Mazid, Y Jiang, W Jia, X Wang, Y Sun, MA Esteban, Q Sun, F Zhou, Z Liu Cynomolgus monkey embryo model captures gastrulation and early pregnancy Cell Stem Cell, 2023-04-06;30(4):362-377.e7. 2023-04-06 [PMID: 37028403] (Bioassay, Primate - Macaca fascicularis (Crab-eating Monkey or Cynomolgus Macaque))
• S Xu, X Yang, Q Chen, Z Liu, Y Chen, X Yao, A Xiao, J Tian, L Xie, M Zhou, Z Hu, F Zhu, X Xu, F Hou, J Nie Leukemia inhibitory factor is a therapeutic target for renal interstitial fibrosis EBioMedicine, 2022-11-04;86(0):104312. 2022-11-04 [PMID: 36335669] (Bioassay, Mouse, Rat)
• Z Li, F Fang, Y Long, Q Zhao, X Wang, Z Ye, T Meng, X Gu, W Xiang, C Xiong, H Li The balance between NANOG and SOX17 mediated by TET proteins regulates specification of human primordial germ cell fate Cell & bioscience, 2022-11-04;12(1):181. 2022-11-04 [PMID: 36333732] (Bioassay, Human)
• SW Wang, MJ Herriges, K Hurley, DN Kotton, AM Klein CoSpar identifies early cell fate biases from single-cell transcriptomic and lineage information Nature Biotechnology, 2022-02-21;0(0):. 2022-02-21 [PMID: 35190690] (Bioassay, Human)
• M Lindkvist, MM Zegeye, M Grenegård, LU Ljungberg Pleiotropic, Unique and Shared Responses Elicited by IL-6 Family Cytokines in Human Vascular Endothelial Cells International Journal of Molecular Sciences, 2022-01-27;23(3):. 2022-01-27 [PMID: 35163371] (Bioassay, Human)
• YC Wen, CL Liu, HL Yeh, WH Chen, KC Jiang, VTN Tram, M Hsiao, J Huang, WY Chen, YN Liu PCK1 regulates neuroendocrine differentiation in a positive feedback loop of LIF/ZBTB46 signalling in castration-resistant prostate cancer British Journal of Cancer, 2021-11-24;0(0):. 2021-11-24 [PMID: 34815524] (Bioassay, Human)
• Y Fan, Z Min, S Alsolami, Z Ma, E Zhang, W Chen, K Zhong, W Pei, X Kang, P Zhang, Y Wang, Y Zhang, L Zhan, H Zhu, C An, R Li, J Qiao, T Tan, M Li, Y Yu Generation of human blastocyst-like structures from pluripotent stem cells Cell Discovery, 2021-09-07;7(1):81. 2021-09-07 [PMID: 34489415] (Bioassay, Human)
• H Wang, S Si, M Jiang, L Chen, K Huang, W Yu Leukemia inhibitory factor is involved in the pathogenesis of NSCLC through activation of the STAT3 signaling pathway Oncology Letters, 2021-07-14;22(3):663. 2021-07-14 [PMID: 34386085] (Bioassay, Human)
• ME Clements, L Holtslande, C Edwards, V Todd, SDR Dooyema, K Bullock, K Bergdorf, CA Zahnow, RM Connolly, RW Johnson HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer Oncogene, 2021-07-10;0(0):. 2021-07-10 [PMID: 34247191] (Bioassay, Human)
• W Yuan, Z Yao, V Veerapandi, X Yang, X Wang, D Chen, L Ma, C Li, Y Zheng, F Luo, XY Zhao The histone demethylase KDM2B regulates human primordial germ cell-like cells specification International journal of biological sciences, 2021-01-01;17(2):527-538. 2021-01-01 [PMID: 33613110] (Bioassay, Human)
• SR Lin, YC Wen, HL Yeh, KC Jiang, WH Chen, N Mokgautsi, J Huang, WY Chen, YN Liu EGFR-upregulated LIFR promotes SUCLG2-dependent castration resistance and neuroendocrine differentiation of prostate cancer Oncogene, 2020-09-22;0(0):. 2020-09-22 [PMID: 32963351] (Bioassay, Human)
• F Fang, Z Li, Q Zhao, C Xiong, K Ni Analysis of multi-lineage gene expression dynamics during primordial germ cell induction from human induced pluripotent stem cells Stem Cell Res Ther, 2020-03-04;11(1):100. 2020-03-04 [PMID: 32127035] (Cell Culture, Human)
• Z Li, F Fang, Q Zhao, H Li, C Xiong Supplementation of vitamin C promotes early germ cell specification from human embryonic stem cells Stem Cell Res Ther, 2019-11-15;10(1):324. 2019-11-15 [PMID: 31730021] (Cell Culture, Human)
• S Viswanadha, Y Luo, GR Sareddy, B Santhamma, M Zhou, M Li, S Ma, R Sonavane, UP Pratap, KA Altwegg, X Li, A Chang, AC Riveros, KV Dileep, KYJ Zhang, X Pan, R Murali, M Bajda, GV Raj, AJ Brenner, V Manthati, MK Rao, RR Tekmal, HB Nair, KJ Nickisch, RK Vadlamudi EC359-A first-in-class small molecule inhibitor for targeting oncogenic LIFR signaling in triple negative breast cancer Mol. Cancer Ther., 2019-05-29;0(0):. 2019-05-29 [PMID: 31142661] (Surface Plasmon Resonance, Human)
• A Tscherner, AC Brown, L Stalker, J Kao, I Dufort, MA Sirard, J LaMarre STAT3 signaling stimulates miR-21 expression in bovine cumulus cells during in vitro oocyte maturation Sci Rep, 2018-08-01;8(1):11527. 2018-08-01 [PMID: 30068990] (Bioassay, Bovine)
• L Alabdi, M He, Q Yang, AB Norvil, H Gowher The transcription factor Vezf1 represses the expression of the antiangiogenic factor d2 in endothelial cells J. Biol. Chem., 2018-05-24;0(0):. 2018-05-24 [PMID: 29794136] (Bioassay, Human)
• H Li, J Yao, X Chang, J Wu, T Duan, K Wang LIFR increases the release of sEng via the up-regulation of MMP14 expression in PE Reproduction, 2018-01-23;0(0):. 2018-01-23 [PMID: 29363569] (Bioassay, Human)
• S Jiao, Y Liu, Y Yao, J Teng miR-124 promotes proliferation and differentiation of neuronal stem cells through inactivating Notch pathway Cell Biosci, 2017-12-11;7(0):68. 2017-12-11 [PMID: 29238518] (Bioassay, Rat)
• H Zhang, F Sun, J Wang, L Xie, C Yang, M Pan, B Shao, GY Yang, SH Yang, Q ZhuGe, K Jin Combining Injectable Plasma Scaffold with Mesenchymal Stem/Stromal Cells for Repairing Infarct Cavity after Ischemic Stroke Aging Dis, 2017-04-01;8(2):203-214. 2017-04-01 [PMID: 28400986] (Bioassay, Human)
• Enrique Armijo Increased susceptibility to a? toxicity in neuronal cultures derived from familial Azheimer&#039;s disease (PSEN1-A246E) induced pluripotent stem cells Neurosci. Lett, 2016-12-26;0(0):. 2016-12-26 [PMID: 28034781] (Bioassay, Human)
• Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow Nat Cell Biol, 2016-09-19;18(10):1078-1089. 2016-09-19 [PMID: 27642788] (Bioassay, Human)
• Hong S, Choi J, Lee S, Park Y, Park K, Lee J, Kim J, Gajulapati V, Goo J, Singh S, Lee K, Kim Y, Im S, Ahn S, Rose-John S, Heo T, Choi Y A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor beta Subunit, Glycoprotein 130. J Immunol, 2015-05-29;195(1):237-45. 2015-05-29 [PMID: 26026064] (Bioassay, Human)
• Geng , Zhe, Li , Ping, Tan , Li, Song , Houyan Targeted Knockdown of RNA-Binding Protein TIAR for Promoting Self-Renewal and Attenuating Differentiation of Mouse Embryonic Stem Cells. Stem Cells Int, 2015-03-31;2015(0):657325. 2015-03-31 [PMID: 25918534] (Bioassay, Mouse)
• Kwofie K, Scott M, Rodrigues R, Guerette J, Radford K, Nair P, Richards C Regulation of IL-17A responses in human airway smooth muscle cells by Oncostatin M. Respir Res, 2015-02-07;16(0):14. 2015-02-07 [PMID: 25849622] (Bioassay, Human)
• Kondo T, Funayama M, Tsukita K, Hotta A, Yasuda A, Nori S, Kaneko S, Nakamura M, Takahashi R, Okano H, Yamanaka S, Inoue H Focal transplantation of human iPSC-derived glial-rich neural progenitors improves lifespan of ALS mice. Stem Cell Reports, 2014-06-26;3(2):242-9. 2014-06-26 [PMID: 25254338] (Bioassay, Human)
• Lapeire L, Hendrix A, Lambein K, Van Bockstal M, Braems G, Van Den Broecke R, Limame R, Mestdagh P, Vandesompele J, Vanhove C, Maynard D, Lehuede C, Muller C, Valet P, Gespach C, Bracke M, Cocquyt V, Denys H, De Wever O Cancer-associated adipose tissue promotes breast cancer progression by paracrine oncostatin M and Jak/STAT3 signaling. Cancer Res, 2014-09-24;74(23):6806-19. 2014-09-24 [PMID: 25252914] (Bioassay, Human)
• Wagener E, Aurich M, Aparicio-Siegmund S, Floss D, Garbers C, Breusing K, Rabe B, Schwanbeck R, Grotzinger J, Rose-John S, Scheller J The amino acid exchange R28E in ciliary neurotrophic factor (CNTF) abrogates interleukin-6 receptor-dependent but retains CNTF receptor-dependent signaling via glycoprotein 130 (gp130)/leukemia inhibitory factor receptor (LIFR). J Biol Chem, 2014-05-06;289(26):18442-50. 2014-05-06 [PMID: 24802752] (Bioassay, Human, Mouse)

Bioinformatics

• Gene Symbol: LIF
• Uniprot:
  • P15018()