Recombinant human SCF protein

Summary

• High purity human protein (Uniprot number: P21583)
• >98%, by SDS-PAGE quantitative densitometry
• Source: Expressed in E. coli
• 18.5 kDa (monomer)
• Animal origin-free (AOF) and carrier protein-free
• Manufactured in Cambridge, UK
• Lyophilized from Acetonitrile/TFA
• Resuspend in water at >100 µg/mL, prepare single-use aliquots, add carrier protein if desired, and store frozen at -20°C or -80°C.

Featured applications

• Maintenance and expansion of hematopoietic stem cells, neural stem cells, and mesenchymal stem cells
• Cancer research, including the SCF/c-kit pathway
• Hematopoietic differentiation to multiple myeloid blood lineages
• Tissue morphogenesis during embryonic development
• Proliferation and migration of cardiac progenitor cells
• Development and maintenance of mast cells, dendritic cells, and T cells

Bioactivity

Purity

Qkine SCF has equivalent bioactivity to SCF from an alternative major supplier

Recombinant SCF activity was determined using proliferation of TF-1 human myeloid leukemia cells. Cells were treated in triplicate with a serial dilution of SCF for 48 hours. Cell viability was measured using the Cell Titer-Glo (Promega) luminescence assay. Data from Qk078 lot #204613. EC50 = Qk078: 2.86 ng/mL (154 pM). Supplier B: 3.05 ng/ml (166 pM)

Protein background

Stem Cell Factor (SCF), also known as kit-ligand or mast cell growth factor, is a pivotal protein in stem cell function, from embryonic development to tissue regeneration and cancer biology [1]. SCF functions primarily through interaction with its receptor, c-kit, a transmembrane tyrosine kinase receptor expressed on the surface of various cell types, including hematopoietic stem cells, neural crest-derived cells, melanocytes, and germ cells. Upon binding to c-kit, it triggers a cascade of intracellular signaling pathways, such as the Ras/MAPK, PI3K/Akt, and JAK/STAT pathways, which regulate cell proliferation, survival, migration, and differentiation [2,3].

Stem Cell Factor serves as a crucial ligand for its receptor, c-Kit, initiating signaling cascades upon binding. SCF can also be processed into a soluble form through proteolytic cleavage near the cell membrane. This cleavage releases the extracellular domain of SCF into the extracellular space, generating soluble SCF. Despite this modification, soluble SCF retains its ability to bind to c-Kit and activate downstream signaling pathways. Soluble SCF may act as a paracrine or autocrine factor, exerting its effects on nearby cells or the same cell producing it [3,4].

One of the key roles of SCF is in hematopoiesis, where SCF acts as a critical factor in the maintenance and expansion of hematopoietic stem cells (HSCs) in the bone marrow microenvironment [5,6]. It not only promotes the self-renewal of HSCs but also facilitates their differentiation into various blood cell lineages, including red blood cells, mast cells, and platelets [4].

Stem Cell Factor plays a crucial role in embryonic development, where it contributes to the formation of various tissues and organs. During embryogenesis, SCF is implicated in the proliferation, migration, and survival of neural crest cells, which give rise to a diverse array of cell types, including neurons, glial cells, melanocytes, and smooth muscle cells [7].

Beyond its roles in normal physiology, dysregulation of SCF signaling is associated with various pathological conditions, including cancer [8]. Aberrant activation of the SCF/c-kit pathway is observed in certain types of cancer, such as gastrointestinal stromal tumors (GISTs), acute myeloid leukemia (AML), and melanoma. In these malignancies, mutations in c-kit or overexpression of SCF contribute to uncontrolled cell proliferation, survival, and metastasis, making the SCF/c-kit axis an attractive target for cancer therapy [9].

Background references

1. Huang EJ, Nocka KH, Buck J, Besmer P. Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2. Mol Biol Cell. 1992;3(3):349-362. https://doi.org/10.1091/mbc.3.3.349
2. Lennartsson J, Rönnstrand L. Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol Rev. 2012;92(4):1619-1649. https://doi.org/10.1152/physrev.00046.2011
3. Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell. 2007;130(2):323-334. doi: 10.1016/j.cell.2007.05.055
4. Huang EJ, Nocka KH, Buck J, Besmer P. Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2. Mol Biol Cell. 1992;3(3):349-362. doi:10.1091/mbc.3.3.349
5. Blume-Jensen P, Janknecht R, Hunter T. The kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136. Curr Biol. 1998;8(13):779-782. https://doi.org/10.1016/s0960-9822(98)70300-2
6. Zsebo KM, Williams DA, Geissler EN, et al. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell. 1990;63(1):213-224. https://doi.org/10.1016/0092-8674(90)90303-v
7. Waskow C, Madan V, Bartels S, et al. Hematopoietic stem cell transplantation without irradiation. Nat Methods. 2009;6(4):267-269. https://doi.org/10.1038/nmeth.1314
8. Hu Y, Smyth GK. ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. J Immunol Methods. 2009;347(1-2):70-78. https://doi.org/10.1016/j.jim.2009.06.008
9. Linnekin D. Early signaling pathways activated by c-Kit in hematopoietic cells. Int J Biochem Cell Biol. 1999;31(10):1053-1074. https://doi.org/10.1016/s1357-2725(99)00076-0

Publications using recombinant human SCF protein (Qk078)

STAT3 signalling enhances tissue expansion during postimplantation mouse development
bioRxiv preprint (2024) by Azami, T. et al.
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