Recombinant Human CD117 (D816F) Protein

Name: Recombinant Human CD117 (D816F) Protein
Brand: Beta LifeScience
SKU: BL-0482SG
Availability: InStock

Collections: All products, Cluster of differentiation (cd) proteins, Featured cd protein molecules, High-quality recombinant proteins

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Product Overview

Tag	GST
Host Species	Human
Accession	NM_000222
Synonym	PBT, SCFR, CD117
Background	c-KIT is a proto-oncogene and a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor). c-KIT was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit. c-KIT together with its ligand regulates growth and activation of a variety of hemopoietic and non-hemopoietic cells. Mutations in c-KIT are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous lukemia, and piebaldism. Recently, deregulation of the KIT receptor TK by the prevalent activation loop mutation D816V has served as a focal point in therapeutic strategies aimed at curbing neoplastic mast cell growth (2).
Description	Recombinant human c-KIT (D816F) (544-end) was produced by baculovirus in Sf9 insect cells, fused with a GST tag at N-terminus. This protein is purified with our unique purification methods.
Source	Sf9 insect cells
AA Sequence	544a.a.-end
Molecular Weight	~73 kDa
Purity	For specific purity information on a given lot, see related COA.
Endotoxin	< 1.0 EU per μg of the protein as determined by the LAL method
Bioactivity	Active
Formulation	Recombinant protein is supplied in 50mM Tris-HCl, pH 7.5, 50mM NaCl, 10mM Glutathione, 0.25mM DTT, 0.1mM EDTA, 0.1mM PMSF and 25% glycerol.
Stability	The recombinant protein is stable for up to 12 months at -70°C
Usage	For Research Use Only
Storage	Recombinant Human CD117 (D816F) Protein should be stored should be stored at < -70°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function	Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.
Subcellular Location	[Isoform 1]: Cell membrane; Single-pass type I membrane protein.; [Isoform 2]: Cell membrane; Single-pass type I membrane protein.; [Isoform 3]: Cytoplasm.
Protein Families	Protein kinase superfamily, Tyr protein kinase family, CSF-1/PDGF receptor subfamily
Database References	HGNC: 6342 OMIM: 164920 KEGG: hsa:3815 STRING: 9606.ENSP00000288135 UniGene: PMID: 29896733 A genetic analysis revealed a novel heterozygous mutation c.645_650delTGTGTC which results in the in-frame deletion of Val216 and Ser217 in the extracellular domain of KIT in case of familial piebaldism. Mutant KIT was able to form a heterodimer with Wt KIT and bind SCF; however, the phosphorylation of KIT, STAT5 and ERK1/2 was markedly decreased. PMID: 29631773 These results suggest that, in leukaemic lymphoblasts, c-Kit triggers a signalling pathway with proliferative and anti-apoptotic effects; information to this effect has not yet been reported in the literature PMID: 29495952 KIT and PDGFRA mutations account for 85-90% of GISTs; subsequent genetic studies have led to the identification of mutation/epimutation of additional genes, including the succinate dehydrogenase (SDH) subunit A, B, C, and D genes. PMID: 29413424 Data show that Kit autophosphorylation is spatio-temporally regulated and may offer a new strategy for treating imatinib-resistant gastrointestinal stromal tumours (GISTs) . PMID: 29196126 combined panel had the highest sensitivity and specificity at 96.3% and 100%, which was significantly or marginally higher than those of EZH2, C-KIT, and CD205 alone PMID: 29487009 The results show that KIT mutations and CD-117 overexpression in vulvar melanomas markers of better progression free survival. PMID: 28734009 current c-Kit reporter models are discussed with respect to myocardial c-Kit cell biology and function. PMID: 28627370 Cytoplasmic membrane CD117 immunoreactivity was demonstrated in only four (15%) out of 27 squamous cell carcinoma of the esophagus and in none of the controls. PMID: 29970514 a D816V-positive result in a screening blood sample identifies systemic mastocytosis among patients with hymenoptera venom-induced anaphylaxis in whom the diagnosis would most probably have been missed PMID: 28432683 PKC-delta expression is associated with KIT expression and the prognosis of patients with adenoid cystic carcinomas (AdCCs), suggesting that PKC-delta may be a potential therapeutic target for AdCCs. PMID: 28561935 Findings show that CD117 is negative in the majority of tumors with superficial features of in-situ or invasive squamous cell carcinoma and deeper, infiltrative islands with glandular differentiation, supporting that cutaneous adenosquamous carcinoma might be closer to being a variant of squamous cell carcinoma than an adnexal carcinoma. PMID: 28766737 Study demonstrates that an oncogenic tyrosine kinase mutant, KIT(D816V), can alter the transcriptional program of the transcription factor MITF in melanoma. PMID: 28584020 High c-kit expression is associated with small cell lung cancer. PMID: 28055980 The expression of c-Kit under the influence of nilotinib, dasatinib, erlotinib, gefitinib and afatinib was studied in HPV-positive head and neck squamous cell carcinomas. Gefitinib significantly increased cKIT expression in HPV-positive and HPV-negative head and neck squamous cell carcinoma cells whereas nilotinib and afatinib decreased cKIT expression in HPV-positive SCC. PMID: 29715092 CD117 can be a useful marker to help differentiate plasmablastic plasma cell myeloma from plasmablastic lymphoma PMID: 28226184 Our findings showed that increased expression of CD34 and CD117 markers confer tumor progression and aggressiveness on prostate cancer. PMID: 28552539 A phase Ib study of dasatinib plus ipilimumab in patients with gastrointestinal stromal tumor (GIST) and other sarcomas was performed on the basis of preclinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic. PMID: 28007774 Mutation in KIT gene is associated with mucosal melanoma. PMID: 28296713 4 different mutant (MT-KIT) KIT proteins from GIST tumors are intrinsically less stable than wild-type KIT due to proteasome-mediated degradation and abnormally localized to the endoplasmic reticulum or the Golgi complex. PKC-theta; is strongly and exclusively expressed in GISTs and interacts with intracellular MT-KIT to promote its stabilization by increased retention in the Golgi complex. PMID: 27440273 Report a new in vivo model of KIT D816V+ advanced systemic mastocytosis developed by transplantation of the human ROSAKIT D816V-Gluc mast cell line in NOD-SCID IL-2R gamma-/- mice, using Gaussia princeps luciferase as a reporter. PMID: 27783996 KIT D816V mutation sensitized mast cells from systemic mastocytosis patients to histone deacetylase inhibitor mediated killing. PMID: 28038453 the presented study demonstrates that CBFB-MYH11-based MRD status during the first 3 months after allo-HCT, but not KIT mutations, can be used to identify patients with a high risk of relapse. PMID: 27650511 we have shown that KIT(+) cells in human, rat, mouse and guinea pig bladder are mast cells and not interstitial cells of Cajal PMID: 27997763 Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression. PMID: 27793025 findings that the CD56 and CD117 expression levels are lower in advanced stages than earlier stages and that LDH level and CD117 expression have an inverse relationship in patients with newly diagnosed multiple myeloma (MM) suggest that CD56 and CD117 expressions may be prognostic markers for MM. PMID: 28270374 Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations PMID: 28327988 activation of KIT by a gain-of-function, somatic mutation is a novel mechanism of resistance to crizotinib in ROS1 rearranged non-small cell lung cancer PMID: 27068398 Mutational activation of Kit-, Ras/Raf/Erk- and Akt- pathways indicate the biological importance of these pathways and their components as potential targets for therapy. PMID: 27391150 KIT exon 11 codons 557-558 deletion enhanced CXCL12-mediated GIST cell migration. PMID: 26936919 Data show the kinetic behavior of a G-rich sequence located within the c-KIT proximal promoter (kit2) in the presence of monovalent cations K+ and Na+. PMID: 29069417 Long-term follow-up of patients with metastatic GIST treated with regorafenib suggests particular benefit among patients with primary KIT exon 11 mutations and those with SDH-deficient GIST. Dose modifications are frequently required to manage treatment-related toxicities PMID: 27371698 To study the mechanism underlying the mixed clinical response, we carried out whole-exome sequencing and targeted longitudinal analysis of cfDNA. This revealed two tumour subclones; one with a KIT mutation that responded to imatinib and a second KIT-wild-type subclone that did not respond to imatinib and a second KIT-wild-type subclone that did not respond to imatinib PMID: 27502704 c-kit-positive cells derived from right atrium tissue were associated with serum BNP PMID: 29151486 For hot spots in KIT and PDGFRA genes, 23 out of 146 KIT/PDGFRA wild-type cases carried mutations according to next-generation sequencing (NGS). PMID: 26848617 KIT and DNMT1 co-expression promotes, whereas dual inactivation of them suppresses, lung cancer cell proliferation and metastatic growth in vitro and in vivo, in a synergistic manner. PMID: 28869603 Data indicate that BRAF, NRAS and C-KIT melanomas constitute distinct clinico-pathological entities. PMID: 29187493 our data established CD117 as a direct target of miR-34-5p and demonstrated that this regulation interferes with several CD117-mediated effects on osteosarcoma cells PMID: 27056900 Results indicate anthraquinone derivative AQ1 as a promising compound for the target therapy of c-KIT-dependent tumors. PMID: 26942875 Data show that afatinib resistant clones were selectively killed by knock down of ERBB3 + c-MET + c-KIT, but not by the individual or doublet knock down combinations, and the combination of afatinib with the SRC family inhibitor dasatinib killed afatinib resistant H1975 cells in a greater than additive fashion. PMID: 26934000 Multivariate analysis confirmed KIT exon 11 deletion (P = 0.003) and clinical risk classification (P < 0.001) as independent adverse prognostic factors for RFS. Intermediate-risk patients harboring KIT exon 11 deletions had RFS outcomes similar to high-risk patients. PMID: 27753268 to establish that, of all KIT mutations, D816 mutation alone is an unfavorable prognostic factor. PMID: 28762080 Podocalyxin-like protein 1 is a relevant marker for human c-kit(pos) cardiac stem cells.( PMID: 23897803 High fertilization (56.06%) and pregnancy (41.7%) rates accomplished in this study following ICSI-AOA indicated that expression profiles of PLCzeta, PAWP, and TR-KIT were low in globozoospermic individuals PMID: 27089467 Different types of cancers harbor mutations in the oncogene KIT PMID: 27216642 KIT knockdown increased RAS/MAPK pathway activation in a BRAF(V600E)-mutant melanoma cell line. PMID: 28947418 Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age 40 years and marrow blast 70% were associated with inferior OS. PMID: 27391574 High KIT expression is associated with drug Resistance in Gastrointestinal Stromal Tumors. PMID: 28760855 the critical physiological role of the KIT-ET3-NO pathway in fulfilling high demand (exceeding basal level) of endothelium-dependent NO generation for coping with atherosclerosis, pregnancy, and aging, is reported. PMID: 28880927 determined that miR-137 can participate in the leukemogenesis by regulating c-kit, which could be used as a therapeutic target for acute myeloid leukemia PMID: 28314168

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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