Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutation at S1 or W loci are characterized by lacks of pigmentation, gametogenesis and hematopoiesis. Stem cell factor and its receptor, which is encoded by c-kit proto-oncogene, play an important role in the survival and proliferation of these primitive cells. Primordial germ cell is maintained and expanded on cells transfected with membrane-bound SCF gene. Pigmentation of mouse embryo is influenced by administration of monoclonal antibody for c-kit product, ACK 2, because of inhibition of melanoblast migration to epidermal tissue. Moreover, hematopoietic progenitors are considered to be maintained and expanded in liquid culture in the presence of SCF and other growth factors. All of these primitive cells express c-kit product and the direct action of SCF is expected. However, two types of SCF, soluble form and membrane-bound form, exist and the physiological significance of these forms in vivo remain unsolved.
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PMID:[Stem cell factor/c-kit interaction in primordial germ cell, melanoblast and hematopoietic progenitors]. 138 68

The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor for stem cell factor (SCF). The c-kit/SCF signal is expected to have an important role in hematopoiesis. A monoclonal antibody (ACK-2) against the murine c-kit molecule was prepared. Flow cytometric analysis showed that the bone marrow cells that expressed the c-kit molecule (approximately 5%) were B220(B)-, TER119(erythroid)-, Thy1negative-low, and WGA+. A small number of Mac-1(macrophage)+ or Gr-1(granulocyte)+ cells were c-kit-low positive. Colony-forming unit in culture (CFU-C) and day-8 and day-12 CFU-spleen (CFU-S) existed exclusively in the c-kit-positive fraction. About 20% of the Lin(lineage)-c-kit+ cells were rhodamine-123low and this fraction contained more day-12 CFU-S than day-8 CFU-S. On the basis of these findings, murine hematopoietic stem cells were enriched with normal bone marrow cells. One of two and one of four Thy-1lowLin-WGA+c-kit+ cells were CFU-C and CFU-S, respectively. Long-term repopulating ability was investigated using B6/Ly5 congenic mice. Eight and 25 weeks after transplantation of Lin-c-kit+ cells, donor-derived cells were found in the bone marrow, spleen, thymus, and peripheral blood. In peripheral blood, T cells, B cells, and granulocyte-macrophages were derived from donor cells. Injection of ACK-2 into the irradiated mice after bone marrow transplantation decreased the numbers of day-8 and day-12 CFU-S in a dose-dependent manner. Day-8 spleen colony formation was completely suppressed by the injection of 100 micrograms ACK-2, but a small number of day-12 colonies were spared. Our data show that the c-kit molecule is expressed in primitive stem cells and plays an essential role in the early stages of hematopoiesis.
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PMID:Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule. 171 68

We have analyzed c-kit expression by hematopoietic progenitors from normal and 5-fluorouracil (5-FU)-treated mice by staining with monoclonal anti-c-kit antibody ACK-4. Marrow cells that were enriched for progenitors by a combination of metrizamide density separation and negative immunomagnetic selection with lineage-specific monoclonal antibodies (MoAbs) were separated into three populations based on the level of c-kit expression, c-kit(high), c-kit(low), and c-kit-. The majority of colony-forming cells from normal mice were in c-kit(high) population, whereas most of the progenitors from 5-FU-treated mice were in the c-kit(low) population. Optimal colony formation from c-kit(low) cells from 5-FU-treated mice required the interactions of at least two factors among interleukin-3 (IL-3), IL-11 and steel factor (SF) whereas colony formation from c-kit(high) cells of normal mice was supported well by IL-3 alone. Blast cells that were derived from 5-day culture of c-kit(low) post 5-FU cells were c-kit(high). These observations suggest that the primitive hematopoietic progenitors in cell cycle dormancy are c-kit(low) whereas actively cell cycling maturer progenitors are c-kit(high). Mature cells, with the exception of mast cells, derived from secondary culture of the c-kit(high) blast cells expressed little, if any, c-kit. These results are consistent with a model in which c-kit expression progresses from low levels on primitive, dormant multipotent progenitors to high levels on later, actively cycling progenitors, and finally, decreases to very low or undetectable levels on most mature blood cells, with the exception of mast cells.
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PMID:Stage-specific expression of c-kit protein by murine hematopoietic progenitors. 769 Dec 57

Interstitial cells of Cajal (ICC) of the guinea-pig small intestine were studied with whole-mount preparations by using the zinc iodide-osmic acid method (ZIO) and immunohistochemistry for vimentin and c-kit receptor tyrosine kinase, and by electron microscopy. The myenteric ICC visualized with ZIO staining are immunopositive to both anti-c-kit antibody (ACK-2) and anti-vimentin antibody (V9), and constitute an independent cellular network from the myenteric plexus. Those cells are characterized by many mitochondria, abundant intermediate filaments, and surface cell membranes not covered with a basal lamina. They are connected with each other by gap junctions at tips of the cytoplasmic processes. It is concluded that the myenteric ICC of the guinea-pig intestine are fibroblast-like cells and that they correspond to the c-kit expressing cells regarded as the intestinal pacemaker.
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PMID:Anti-c-kit protein immunoreactive cells corresponding to the interstitial cells of Cajal in the guinea-pig small intestine. 894 37

Initiation of folliculogenesis through the induction of primordial follicle development in the ovary has an important role in determining the fertility and reproductive fitness of most mammalian species. The factors that control this critical process are largely unknown. The hypothesis tested in the current study was that kit-ligand/stem cell factor (KL) promotes the initiation and progression of primordial follicle development in the ovary. Ovaries from 4-day-old rats were maintained in organ culture for 5 and 14 days and treated with no factor (control), recombinant kit-ligand (KL), or gonadotropins (FSH and hCG). Follicles in ovarian sections were counted and histologically classified as primordial (stage 0), early primary (stage 1), primary (stage 2), transitional (stage 3), or preantral (stage 4). Fresh ovaries from 4-day-old rats contained 68% primordial follicles (stage 0) and 32% developing follicles (stages 1-4) per section. After 5 and 14 days in culture, section from control ovaries contained approximately 41% and 55%, respectively, developing follicles (stage 1-4) per section due to spontaneous development of primordial follicles. Spontaneous primordial follicle development was completely blocked by ACK-2, a c-kit antibody that blocks KL actions. This observation suggests that endogenous KL is necessary for primordial follicle development in vitro. After 14 days of KL treatment, sections from ovaries contained 17% primordial follicles (stage 0) and 83% developing follicles (stage 1-4) per section demonstrating a dramatic induction of primordial follicle development by KL. Gonadotropins (FSH and hCG) did not induce primordial follicle development but did increase the percentage of preantral follicles (stage 4) per section. This small increase in preantral follicles in response to gonadotropins was blocked by ACK-2 suggesting that KL may in part mediate gonadotropin actions after the initiation of primordial follicle development. Ovaries contained an average of 309+/-10 follicles per section. The total number of follicles per section did not significantly vary between treatments suggesting that the effects of KL were not due to an alteration in follicle number (i.e. survival). KL appears to be one of the first factors identified to be involved in the promotion of primordial follicle development. Results suggest that KL is necessary and sufficient to induce primordial follicle development and initiate folliculogenesis.
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PMID:Kit-ligand/stem cell factor induces primordial follicle development and initiates folliculogenesis. 1046

Stem cell factor (SCF) plays an important role in migration, adhesion, proliferation, and survival of primordial germ cells and spermatogonia during testicular development. However, the function of SCF in the adult testis is poorly described. We have previously shown that, in the presence of SCF, there were more type A spermatogonia incorporating thymidine at stage XII of rat seminiferous tubules cultured in vitro than in the absence of SCF, implying that the increased DNA synthesis might result from enhanced survival of spermatogonia. To explore the potential pro-survival function of SCF during spermatogenesis, the seminiferous tubules from stage XII were cultured in the presence or absence of SCF (100 ng/ml) for 8, 24, 48, and 72 hours, respectively, and apoptosis was analyzed by DNA laddering and in situ 3'-end labeling (ISEL) staining. Surprisingly, not only spermatogonia, but also spermatocytes and spermatids, were protected from apoptosis in the presence of SCF. Apoptosis took place much later and was less severe in the SCF-treated tubules than in the controls. Based on previous studies showing that FSH prevents germ cells from undergoing apoptosis in vitro, and that SCF level is increased dramatically in response to FSH stimulation, we also tested if the pro-survival effect of FSH is mediated through SCF by using a function-blocking monoclonal antibody, ACK-2, to block SCF/c-kit interaction. After 24 hours of blockade, the protective effect of FSH was partially abolished, as manifested by DNA laddering and ISEL analyses. The present study demonstrates that SCF acts as an important survival factor for germ cells in the adult rat testis and FSH pro-survival effect on germ cells is mediated partially through the SCF/c-kit pathway.
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PMID:Stem cell factor protects germ cells from apoptosis in vitro. 1059 35

The significance of the interaction between Sertoli cell-produced stem cell factor (SCF) and its receptor, c-kit, on Leydig cells (LCs) during LC development and differentiation is unknown. In the present study, we investigated the potential role of the SCF/c-kit system in LC apoptosis and precursor LC proliferation after ethylene dimethane sulfonate (EDS) treatment in rats. A function-blocking anti-c-kit antibody, ACK-2, was used to block SCF/c-kit interaction at four time points, corresponding to the peak of LC apoptosis and three waves of proliferation of precursor LCs. Blockade of SCF/c-kit interaction by ACK-2 accelerated LC apoptosis and inhibited proliferation of precursor LCs during the first two waves of precursor LC proliferation around days 3-4 and day 10, but not the third wave of precursor LC proliferation around day 20 after EDS treatment. The data suggest that the soluble SCF might act as a survival factor for mature LCs and a growth factor for precursor LCs after EDS-induced LC depletion. This is also supported by a close correlation between the oscillating levels of soluble SCF mRNA and the profiles of LC apoptosis and regeneration. Since regeneration of the LC population after EDS treatment resembles the development of adult-type LCs during prepubertal life, the present findings imply that soluble SCF might participate in regulation of the formation of the LC population during testicular development. Our data also support a model in which delicate and reciprocal regulation exists between soluble SCF production by Sertoli cells, testosterone production by LCs, and pituitary gonadotropins.
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PMID:Stem cell factor functions as a survival factor for mature Leydig cells and a growth factor for precursor Leydig cells after ethylene dimethane sulfonate treatment: implication of a role of the stem cell factor/c-Kit system in Leydig cell development. 1107 85