Stem cell factor (SCF), a novel hematopoietic growth factor and ligand for c-kit tyrosine kinase receptor, maps on human chromosome 12 between 12q14.3 and 12qter

1991 ◽  
Vol 17 (2) ◽  
pp. 207-214 ◽  
Author(s):  
Edwin N. Geissler ◽  
Martha Liao ◽  
J. David Brook ◽  
Francis H. Martin ◽  
Krisztina M. Zsebo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Human Chromosome ◽  
Stem Cell Factor ◽  
Chromosome 12 ◽  
Tyrosine Kinase Receptor ◽  
Hematopoietic Growth Factor

Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor

Cell ◽  
1990 ◽  
Vol 63 (1) ◽  
pp. 213-224 ◽  
Author(s):  
Krisztina M. Zsebo ◽  
David A. Williams ◽  
Edwin N. Geissler ◽  
Virginia C. Broudy ◽  
Francis H. Martin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Tyrosine Kinase Receptor

scholarly journals The c-kit receptor ligand functions as a mast cell chemoattractant

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 958-963 ◽  
Author(s):  
CJ Meininger ◽  
H Yano ◽  
R Rottapel ◽  
A Bernstein ◽  
KM Zsebo ◽  
...  
Keyword(s):  
Mast Cell ◽  
Growth Factor ◽  
Mast Cells ◽  
Tyrosine Kinase ◽  
Cell Motility ◽  
Stem Cell Factor ◽  
Tissue Type ◽  
Tyrosine Kinase Receptor ◽  
Directed Migration ◽  
Kit Receptor

Mast cells accumulate at sites of neovascularization, solid tumors, and many immune reactions. Such accumulation requires directed migration of mature mast cells or their precursors. The nature of the chemoattractants that regulate mast cell motility and the identity of the receptors that mediate the chemotactic response are poorly understood. We have tested the ability of stem cell factor (SCF), a mast cell growth factor, to stimulate mast cell migration. Our results show that SCF is a potent mast cell attractant that stimulates directional motility of both mucosal and connective tissue-type mast cells. The activity is potentiated by costimulation with interleukin-3 (IL-3), another mast cell chemoattractant. SCF, a known ligand for the c-kit tyrosine kinase receptor, was unable to stimulate motility in W42 mutant mast cells, which have a defective c-kit tyrosine kinase. However, W42 mast cells were still able to migrate in response to IL-3. These results show that SCF is a chemotactic factor as well as a growth factor and that the c-kit receptor can transduce signals leading to both cell proliferation and increased directional cell motility.

scholarly journals The c-kit receptor ligand functions as a mast cell chemoattractant

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 958-963 ◽  
Author(s):  
CJ Meininger ◽  
H Yano ◽  
R Rottapel ◽  
A Bernstein ◽  
KM Zsebo ◽  
...  
Keyword(s):  
Mast Cell ◽  
Growth Factor ◽  
Mast Cells ◽  
Tyrosine Kinase ◽  
Cell Motility ◽  
Stem Cell Factor ◽  
Tissue Type ◽  
Tyrosine Kinase Receptor ◽  
Directed Migration ◽  
Kit Receptor

Abstract Mast cells accumulate at sites of neovascularization, solid tumors, and many immune reactions. Such accumulation requires directed migration of mature mast cells or their precursors. The nature of the chemoattractants that regulate mast cell motility and the identity of the receptors that mediate the chemotactic response are poorly understood. We have tested the ability of stem cell factor (SCF), a mast cell growth factor, to stimulate mast cell migration. Our results show that SCF is a potent mast cell attractant that stimulates directional motility of both mucosal and connective tissue-type mast cells. The activity is potentiated by costimulation with interleukin-3 (IL-3), another mast cell chemoattractant. SCF, a known ligand for the c-kit tyrosine kinase receptor, was unable to stimulate motility in W42 mutant mast cells, which have a defective c-kit tyrosine kinase. However, W42 mast cells were still able to migrate in response to IL-3. These results show that SCF is a chemotactic factor as well as a growth factor and that the c-kit receptor can transduce signals leading to both cell proliferation and increased directional cell motility.

scholarly journals Structure-based design of some quinazoline derivatives as epidermal growth factor receptor inhibitors

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Muhammad Tukur Ibrahim ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Pharmacokinetic Profile ◽  
Egfr Inhibitors ◽  
Tyrosine Kinase Receptor ◽  
Egfr Tyrosine Kinase ◽  
Epidermal Growth

Abstract Background The discovery of epidermal growth factor receptor (EGFR) inhibitors for the treatment of lung cancer, most especially non-small cell lung cancer (NSCLC), was one of the major challenges encountered by the medicinal chemist in the world. The treatment of EGFR tyrosine kinase to manage NSCLCs becomes an urgent therapeutic necessity. NSCLC was the foremost cause of cancer mortality worldwide. Therefore, there is a need to develop more EGFR inhibitors due to the development of drug resistance by the mutation. This research is aimed at designing new EGFR inhibitors using a structure-based design approach. Structure-based drug design comprises several steps such as protein structure retrieval and preparation, ligand library preparation, docking, and structural modification on the best hit compound to design new ones. Result Molecular docking virtual screening on fifty sets of quinazoline derivatives/epidermal growth factor receptor inhibitors against their target protein (EGFR tyrosine kinase receptor PDB entry: 3IKA) and pharmacokinetic profile predictions were performed to identify hit compounds with promising affinities toward their target and good pharmacokinetic profiles. The hit compounds identified were compound 6 with a binding affinity of − 9.3 kcal/mol, compounds 5 and 8, each with a binding affinity of − 9.1 kcal/mol, respectively. The three hit compounds bound to EGFR tyrosine kinase receptor via four different types of interactions which include conventional hydrogen bond, carbon-hydrogen bond, electrostatic, and hydrophobic interactions, respectively. The best hit (compound 6) among the 3 hit compounds was retained as a template and used to design sixteen new EGFR inhibitors. The sixteen newly designed compounds were also docked into the active site of EGFR tyrosine kinase receptor to study their mode of interactions with the receptor. The binding affinities of these newly designed compounds range from − 9.5 kcal/mol to − 10.2 kcal/mol. The pharmacokinetic profile predictions of these newly designed compounds were further examined and found to be orally bioavailable with good absorption, low toxicity level, and permeable properties. Conclusion The sixteen newly designed EGFR inhibitors were found to have better binding affinities than the template used in the designing process and afatinib the positive control (an FDA approved EGFR inhibitor). None of these designed compounds was found to violate more than the permissible limit set by RO5. More so, the newly designed compounds were found to have good synthetic accessibility which indicates that these newly designed compounds can be easily synthesized in the laboratory.

scholarly journals The rat c-kit ligand, stem cell factor, induces c-kit receptor-dependent mouse mast cell activation in vivo. Evidence that signaling through the c-kit receptor can induce expression of cellular function.

1992 ◽  
Vol 175 (1) ◽  
pp. 245-255 ◽  
Author(s):  
B K Wershil ◽  
M Tsai ◽  
E N Geissler ◽  
K M Zsebo ◽  
S J Galli
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Tyrosine Kinase Receptor ◽  
Kit Ligand ◽  
Kit Receptor

Interactions between products of the mouse W locus, which encodes the c-kit tyrosine kinase receptor, and the Sl locus, which encodes a ligand for c-kit receptor, which we have designated stem cell factor (SCF), have a critical role in the development of mast cells. Mice homozygous for mutations at either locus exhibit several phenotypic abnormalities including a virtual absence of mast cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation of normal mast cells in vitro or in vivo, and also can result in repair of the mast cell deficiency of Sl/Sld mice in vivo. We now report that administration of SCF intradermally in vivo results in dermal mast cell activation and a mast cell-dependent acute inflammatory response. This effect is c-kit receptor dependent, in that it is not observed when SCF is administered to mice containing dermal mast cells expressing functionally inactive c-kit receptors, is observed with both glycosylated and nonglycosylated forms of SCF, and occurs at doses of SCF at least 10-fold lower on a molar basis than the minimally effective dose of the classical dermal mast cell-activating agent substance P. These findings represent the first demonstration in vivo that a c-kit ligand can result in the functional activation of any cellular lineage expressing the c-kit receptor, and suggest that interactions between the c-kit receptor and its ligand may influence mast cell biology through complex effects on proliferation, maturation, and function.

P–314 Serum Stem Cell Factor as a predictor of top quality blasotcysts formation in women with endometriosis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Liss ◽  
M Kuczynska ◽  
A Knight ◽  
K Lukaszuk
Keyword(s):  
Stem Cell ◽  
Ovarian Stimulation ◽  
Stem Cell Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tyrosine Kinase Receptor ◽  
Target Cells ◽  
Serum Samples ◽  
The Mean ◽  
Ovary Reserve

Abstract Study question To evaluate the correlation between the serum level of stem cell factor (s-SCF) during the stimulation and results of embryo culture. Summary answer The serum SCF concentration at the stimulation stage may be a potential predictor of IVF outcome in endometriosis patients. What is known already Stem cell factor (SCF) is a pleiotropic cytokine that affects the target cells via the c-kit receptor, a tyrosine kinase receptor. Recent evidence indicates that SCF and c-kit may play a role in regulation and growth of ovarian follicular function. It is unclear whether endometriosis primarily affects in vitro fertilization outcomes via oocyte quality. SCF is produced during the human follicular phase, immediately before the ovulatory phase, and may play an important role in folliculogenesis and in the mechanism of ovulation. It may reflect a successful stimulation with ample follicle maturation. Study design, size, duration This was a prospective case-control study and consisted four group of patients: 10 with endometriosis, 24 PCOs, 20 with normal (AMH 1.2–4.0 ng/ml) and 11 with lower (AMH<1.2 ng/ml) ovary reserve who were undergoing IVF treatment with the assessment of serum SCF concentration between August 2019 and March 2020 at INVICTA Fertility Centre, Poland. The age of the patients ranged from 22 to 42 years (median 34 years). Participants/materials, setting, methods s-SCF was measured in duplicate by enzyme-linked immunosorbent assay (ELISA) kit in 195 serum samples collected during ovarian stimulation on days 1 and 8 and on the day of oocyte retrieval. We analysed correlation between s-SCF level and formation of top quality (TQ) blastocysts on day 5 formation in the study groups. Main results and the role of chance We have compared mean level of s-SCF within each group dividing the patients into two subgroups – those with at least one TQ blastocyst (TQ) on day 5 vs. those with no TQ blastocysts (no-TQ). There were no significant differences in mean s-SCF level on day 1 of stimulation between no-TQ and TQ patients in PCOs, normal and lower ovary reserve groups (41.1 pg/ml vs. 40.9 pg/ml; 34.8 pg/ml vs. 38.9 pg/ml and 32.3pg/ml vs. 28.7 pg/ml respectively). The mean level of s-SCF in endometriosis patients was higher in case of no-TQ compared to the TQ subgroup and were 41.1 pg/ml and 29.1 pg/ml respectively. Also no significant differences were also observed in the mean level of s-SCF in the no-TQ and TQ subgroups on the 8 day of stimulation and pick-up in PCOs, normal and lower ovary reserve patients. However, again in the case of endometriosis patients, the mean level of s-SCF was significantly lower on the 8 day of stimulation (28.1 pg/ml vs. 49.1 pg/ml; p < 0.05) and pick-up day (33.4 pg/ml vs. 50.4 pg/ml; p < 0.005) in samples from patients who had at least one TQ blastocysts on day 5 of culture. Limitations, reasons for caution More data are required to confirm the corelation of s-SCF level and presence of top quality blastocysts in patients with endometriosis. Wider implications of the findings: Our study suggests that the level of serum SCF during ovarian stimulation in patients with endometriosis of less 30 pg/ml may potentially be a predictor for the chance of obtaining at least one top quality blastocyst on day 5 and thus a chance to successful treatment. Trial registration number Not applicable

Sign in / Sign up

Export Citation Format

Share Document