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 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

scholarly journals Stem cell factor retards differentiation of normal human erythroid progenitor cells while stimulating proliferation

Blood ◽  
1995 ◽  
Vol 86 (2) ◽  
pp. 572-580 ◽  
Author(s):  
K Muta ◽  
SB Krantz ◽  
MC Bondurant ◽  
CH Dai
Keyword(s):  
Stem Cell ◽  
Cell Viability ◽  
Progenitor Cells ◽  
Stem Cell Factor ◽  
Single Cells ◽  
Erythroid Differentiation ◽  
Tyrosine Kinase Receptor ◽  
Total Production ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

Stem cell factor (SCF), the ligand for the c-kit tyrosine kinase receptor, markedly stimulates the accumulation of erythroid progenitor cells in vitro. We now report that SCF delays erythroid differentiation among the progeny of individual erythroid progenitors while greatly increasing the proliferation of these progeny. These effects appear to be independent of an effect on maintenance of cell viability. Highly purified day-6 erythroid colony-forming cells (ECFC), consisting mainly of colony-forming units-erythroid (CFU-E), were generated from human peripheral blood burst-forming units-erythroid (BFU-E). Addition of SCF to the ECFC in serum-free liquid culture, together with erythropoietin (EP) and insulin-like growth factor 1 (IGF-1), resulted in a marked increase in DNA synthesis, associated with a delayed peak in cellular benzidine positivity and a delayed incorporation of 59Fe into hemoglobin compared with cultures without SCF. In the presence of SCF, the number of ECFC was greatly expanded during this culture period, and total production of benzidine-positive cells plus hemoglobin synthesis were ultimately increased. To determine the effect of SCF on individual ECFC, single-cell cultures were performed in both semisolid and liquid media. These cultures demonstrated that SCF, in the presence of EP and IGF-1, acted on single cells and their descendants to delay erythroid differentiation while substantially stimulating cellular proliferation, without an enhancement of viability of the initial cells. This was also evident when the effect of SCF was determined using clones of ECFC derived from single BFU-E. Our experiments demonstrate that SCF acts on individual day-6 ECFC to retard erythroid differentiation while simultaneously providing enhanced proliferation by a process apparently independent of an effect on cell viability or programmed cell death.

Stem cell factor induces phosphatidylinositol 3′-kinase–dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3406-3413 ◽  
Author(s):  
Thamar B. van Dijk ◽  
Emile van den Akker ◽  
Martine Parren-van Amelsvoort ◽  
Hiroyuki Mano ◽  
Bob Löwenberg ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Hematopoietic Cells ◽  
Sh2 Domain ◽  
Stable Complex ◽  
Phosphatidylinositol 3 Kinase ◽  
Sh2 Domains ◽  
And Migration ◽  
Phosphatidylinositol 3

Stem cell factor (SCF) has an important role in the proliferation, differentiation, survival, and migration of hematopoietic cells. SCF exerts its effects by binding to cKit, a receptor with intrinsic tyrosine kinase activity. Activation of phosphatidylinositol 3′-kinase (PI3-K) by cKit was previously shown to contribute to many SCF-induced cellular responses. Therefore, PI3-K-dependent signaling pathways activated by SCF were investigated. The PI3-K-dependent activation and phosphorylation of the tyrosine kinase Tec and the adapter molecule p62Dok-1 are reported. The study shows that Tec and Dok-1 form a stable complex with Lyn and 2 unidentified phosphoproteins of 56 and 140 kd. Both the Tec homology and the SH2 domain of Tec were identified as being required for the interaction with Dok-1, whereas 2 domains in Dok-1 appeared to mediate the association with Tec. In addition, Tec and Lyn were shown to phosphorylate Dok-1, whereas phosphorylated Dok-1 was demonstrated to bind to the SH2 domains of several signaling molecules activated by SCF, including Abl, CrkL, SHIP, and PLCγ-1, but not those of Vav and Shc. These findings suggest that p62Dok-1 may function as an important scaffold molecule in cKit-mediated signaling.

scholarly journals Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo.

1996 ◽  
Vol 183 (6) ◽  
pp. 2681-2686 ◽  
Author(s):  
J J Costa ◽  
G D Demetri ◽  
T J Harrist ◽  
A M Dvorak ◽  
D F Hayes ◽  
...  
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Serum Levels ◽  
Human Mast Cell ◽  
Tyrosine Kinase Receptor ◽  
Kit Ligand ◽  
Wheal And Flare

Stem cell factor (SCF), also known as mast cell growth factor, kit ligand, and steel factor, is the ligand for the tyrosine kinase receptor (SCFR) that is encoded by the c-kit proto-oncogene. We analyzed the effects of recombinant human SCF (r-hSCF, 5-50 micrograms/kg/day, injected subcutaneously) on mast cells and melanocytes in a phase I study of 10 patients with advanced breast carcinoma. A wheal and flare reaction developed at each r-hSCF injection site; by electron microscopy, most dermal mast cells at these sites exhibited extensive, anaphylactic-type degranulation. A 14-d course of r-hSCF significantly increased dermal mast cell density at sites distant to those injected with the cytokine and also increased both urinary levels of the major histamine metabolite, methyl-histamine, and serum levels of mast cell alpha-tryptase. Five subjects developed areas of persistent hyperpigmentation at r-hSCF injection sites; by light microscopy, these sites exhibited markedly increased epidermal melanization and increased numbers of melanocytes. The demonstration that r-hSCF can promote both the hyperplasia and the functional activation of human mast cells and melanocytes in vivo has implications for our understanding of the role of endogenous SCF in health and disease. These findings also indicate that the interaction between SCF and its receptor represents a potential therapeutic target for regulating the numbers and functional activity of both mast cells and cutaneous melanocytes.

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