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

In previous studies, we have characterized the nature and function of the proto-oncogene c-kit, which encodes a receptor tyrosine kinase. This receptor together with its ligand, a stem cell growth factor, constitutes a cell signaling system which is crucial for the development of hematopoietic, melanocytic and germ cells. The expression of the gene correlates with its protein functions in specific cell lineages and is temporally and spatially regulated during fetal and adult life. As a start point to study the gene regulation, we have characterized the promoter of the c-kit gene. A single transcription initiation site located 58 bases upstream of the ATG start codon has been identified. The sequence upstream to the initiation site reveals a TATA-less, non-GC rich promoter. Several potential binding sites for transcription factors pertinent to c-kit expression, such as Sp-1, GATA-1, myb and Oct-4, have been identified. Promoter activities of different lengths of the 5' sequence have been analyzed in transient expression assay. The 2.7 kb of the 5' sequence facilitates the expression of the CAT gene in several cell lines while the sequence further upstream from 2.7 to 5.0 kb shows a negative regulatory activity. This study reveals a unique promoter of the c-kit gene and provides a basis for further elucidation of the regulatory mechanism of c-kit gene expression.
 ...
PMID:Characterization of the promoter of the proto-oncogene c-kit. 753 32

Studies of mice containing mutations in the genes for a receptor tyrosine kinase, c-kit, or its cognate ligand, Steel factor (SLF), establish that this signaling pathway is required for the development of melanocytes from their precursors in the embryonic neural crest (NC). In order to define the mechanism of this requirement, we have labeled cells expressing c-kit with an anti-c-kit antibody (ACK2) and studied the action of SLF on these cells in cultures of murine trunk NC. c-kit positive (c-kit+) cells first appeared after 2 days in culture and were morphologically indistinguishable from other NC cells. These cells subsequently expressed tyrosinase-related protein, an early marker for the melanocyte lineage, and became pigmented in the presence of a phorbol ester. Further, elimination of the c-kit+ population, by incubating the cultures in ACK2, resulted in the ablation of the melanocyte population, but had no effect on the generation of other neural crest derivatives. These data indicate that c-kit+ cells arising from the neural crest are melanocyte progenitors. The addition of SLF to these cultures stimulated an increase in the number of c-kit+ cells, and further studies indicated that SLF acts as both a survival and a proliferative factor for c-kit+ cells. These findings provide a mechanism of regulation of melanocyte development, whereby c-kit is exclusively expressed by melanocyte progenitors within the neural crest precursor population, and subsequent survival and proliferation of these progenitors is regulated by SLF.
 ...
PMID:Steel factor directs melanocyte development in vitro through selective regulation of the number of c-kit+ progenitors. 754 Jan 55

Previously, we showed that c-kit receptor tyrosine kinase is expressed by a subpopulation of dorsal root ganglion (DRG) neurons, and that the ligand for the c-kit receptor, stem cell factor (SCF), induces the neurite outgrowth and supports the survival of these neurons in culture [16]. However, it is unknown which class of DRG neurons express c-kit receptor and which factor regulates differentiation and survival of c-kit-positive neurons. In the present study, we attempted to characterize c-kit positive neurons in the mouse DRG. The c-kit-positive neurons were small or medium in size, and 44% of these neurons contained substance P. Central fibers of the c-kit-positive neurons terminated in laminae I and II of the gray matter of the spinal cord. These results suggest that c-kit-positive neurons in the DRG belong to a functional subpopulation. The c-kit receptor protein was presented on the membrane of processes and growth cones in neurons. When DRG cells of embryonic day 15.5 or 17.5 were cultured, the survival of c-kit-positive neurons was supported by SCF, nerve growth factor (NGF) or leukemia inhibitory factor. SCF and NGF synergistically supported the survival of c-kit-positive neurons at submaximal concentrations. c-kit-positive DRG neurons from neonatal mice survived without addition of any factor in culture, suggesting that the requirement for trophic support in c-kit-positive neurons changes during development.
 ...
PMID:Characterization of c-kit-positive neurons in the dorsal root ganglion of mouse. 754 20

Signaling through the c-kit receptor tyrosine kinase (Kit) is essential for development and survival of mast cells but not of basophils. Moreover, we recently found an activation mutation of Kit in several tumor mast cell lines.
 ...
PMID:Regulation of development, survival and neoplastic growth of mast cells through the c-kit receptor. 754 2

An important goal for the investigation of the proliferation of mammalian cells is to establish a fully defined condition for culturing them in vitro. Here, we report establishment of a fully defined culture condition that supports the primary culture of normal c-kit+IL-7 receptor (IL-7R)+ B precursor cells without the aid of stromal cell lines. This defined culture condition contains IL-7, the ligand for c-kit, transferrin, insulin, and bovine serum albumin as protein components. By using the cell lines derived from RAG2(-/-) mice, which do not differentiate into c-kit- stage, we have evaluated the role of each protein in the cell cycle progression of c-kit+IL-7R+ B precursor cells. Since B precursor cells can grow without insulin, c-kit remains a sole functional receptor tyrosine kinase for their growth. While both c-kit ligand (KL) and IL-7 are the requisite molecules for sustained proliferation of B precursor cells, each molecule plays distinct roles. IL-7 starvation results in prompt arrest of the cells at G1. An accumulation of the cells in the mitotic phase was also detected. Thus, the major role of IL-7 is to regulate the G1/S transition and the process of cytokinesis of B precursor cells. Although prolonged KL starvation over 48 h resulted in accumulation of G1 cells, its effect could not be detected within 24 h, which is long enough for all the cells to complete one cell cycle. This suggests that KL might be involved in the cell cycle progression of B precursor cells in a manner that its signal could still be effective in the one or two cell cycles that follow. Although molecular nature of the signals underlying the present observation awaits future investigation, the method described in this report would provide a useful model system for investigating the signaling pathways that are involved in the cell cycle progression of B precursor cells.
 ...
PMID:Cell cycle control of c-kit+IL-7R+ B precursor cells by two distinct signals derived from IL-7 receptor and c-kit in a fully defined medium. 754 34

The c-kit ligand (KL), a ligand for the c-kit protooncogene receptor tyrosine kinase, is an important regulator of germ cell development in rodent gonads. However, no information about the role of KL in the ovaries of women or higher primates has been available. We studied the expression of KL messenger RNA (mRNA) in human ovaries and the effect of purified hCG and recombinant human FSH (rhFSH) on KL mRNA steady state levels in cultures of human granulosa-luteal (GL) cells obtained at oocyte harvest for in vitro fertilization. KL complementary DNA was generated by reverse transcription-polymerase chain reaction from human ovarian tissue RNA. Two alternatively spliced KL transcripts encoding 248-amino acid (aa) and 220-aa membrane-associated KL proteins were observed in GL cells and ovarian tissue. In Northern blot analysis of human ovarian and GL cell RNA, a major transcript of approximately 6.0 kilobases was detected. Specific mRNA transcripts for KL were detected in dot blot filter hybridization analyses, and the steady state levels of these mRNAs were lowered in cultured GL cells by both gonadotropins in a distinct time- and concentration-dependent manner. The KL mRNA levels of untreated and hCG- or rhFSH-stimulated GL cells were determined at 2- to 3-day intervals between days 2-10 of culture. An 8-h treatment with hCG was shown to decrease KL mRNA levels on days 2, 3, 5, and 7 of culture, whereas rhFSH decreased KL mRNA levels on days 5 and 7 of culture. Time-course and concentration-dependence studies were performed on days 2-7 of culture. Both gonadotropins decreased KL mRNA levels as early as 2 h after treatment. The maximal response to hCG and rhFSH treatment was observed at 7-24 h. Concentration-dependence studies performed 8 or 24 h after treatment indicated that the maximal inhibition occurred with 10-100 ng/ml hCG and 100-300 ng/ml rhFSH. We conclude that 1) the KL transcripts encoding 248- and 220-aa transmembrane proteins are expressed in vivo in the human ovary and in cultured human GL cells; and 2) KL transcript levels are rapidly decreased by gonadotropins in a time- and concentration-dependent manner in cultured GL cells. Thus, KL expression is hormonally regulated in human granulosa cells, and this growth factor may control the function of the ovarian follicle during the human menstrual cycle.
 ...
PMID:Expression of c-kit ligand messenger ribonucleic acids in human ovaries and regulation of their steady state levels by gonadotropins in cultured granulosa-luteal cells. 754 3

The mouse W locus encodes Kit, the receptor tyrosine kinase for stem cell factor (SCF). Kit is required for several developmental processes, including the proliferation and survival of melanoblasts. Because of the nearly complete failure of Wrio/+ melanoblasts to colonize the skin, the costs of Wrio/+ mice are characterized by a majority of white hairs interspersed among pigmented hairs, giving a roan effect. However, 3.6% of Wrio/+ mice exhibit phenotypic reversions, i.e., spots of wild-type color on their coats with an otherwise mutant phenotype. Melanocyte cell lines were derived from each of six independent reversion spots on the skin of (C57BL/6 x DBA/2)F1 Wrio/+ mice. All six melanocyte cell lines exhibited the general characteristics common to normal, nonimmortal mouse melanocytes. Of these, three revertant cell lines had lost the dominant-negative Wrio allele following mitotic recombination between the centromere and the W locus. One of the cell lines remained Wrio/+ but showed (i) stimulation in response to SCF and (ii) increased Kit expression, suggesting that the Wrio mutation can be rescued by increased endogenous expression of the c-kit proto-oncogene. Finally, two cell lines showed no detectable genetic change at the W/Kit locus and failed to respond to SCF stimulation in vitro. These results demonstrate that mitotic recombination can create large patches of wild-type hair on the coats of Wrio/+ mutant mice. This shows that mitotic recombination occurs spontaneously in normal healthy tissue in vivo. Moreover, these experiments confirm that other mechanisms, not associated with loss of heterozygosity, may account for the coat color reversion phenotype.
 ...
PMID:Phenotypic reversions at the W/Kit locus mediated by mitotic recombination in mice. 756 42

In mice, the Kit receptor tyrosine kinase and its ligand, Steel factor, are required for melanogenesis, hematopoesis and gametogenesis We have identified a Xenopus gene, Xkl-1 (Xenopus Kit-like-1) whose predicted protein has striking sequence identity in the catalytic domain and kinase insert to that of c-kit. Xkl-1 is expressed only in dorsal tissues such as the nervous system, notochord and somites of neurulae. Ultraviolet irradiated embryos and animal caps treated with basic FGF unexpectedly express Xkl-1, since they are considered to develop only ventral type tissues. These observations raise the hypothesis that Xkl-1 is involved in Xenopus dorsal development and that dorsal tissues inhibit the expression of Xkl-1 in ventral structures.
 ...
PMID:Expression of Xkl-1, a Xenopus gene related to mammalian c-kit, in dorsal embryonic tissue. 760 52

The development of melanoblasts in normally pigmented and dominant spotting (W) embryos was followed by in situ hybridisation to TRP-2/DT mRNA, which labels migratory melanoblasts from 10 days post coitum. Numerous melanoblasts migrate to the inner ear around 11 days. In contrast, few migratory melanoblasts are associated with the eye or skin at this stage and melanoblasts distribution within the trunk and tail is patchy. The distribution of melanoblasts in 10.5-11-day-old Wv/Wv, Wsh/Wsh and W41/W41 mutants was similar to that in controls but melanoblasts density was lower and by 12 days was severely reduced. These results suggest that mutations of the c-kit receptor tyrosine kinase encoded at the W locus do not alter early migration or differentiation of melanoblasts but severely affect melanoblasts survival.
 ...
PMID:Mutations at the W locus affect survival of neural crest-derived melanocytes in the mouse. 761 26

The mammalian c-kit receptor tyrosine kinase gene is required during embryogenesis for the survival and/or proliferation of three migrating stem cell populations: primordial germ cells, haematopoietic stem cells and neural crest-derived melanoblasts. We have cloned a Xenopus gene, XKrk1, whose closest relative is c-kit. Differences in the expression pattern suggest that XKrk1 is not the Xenopus homologue of c-kit; however, it is expressed in a migrating stem cell population, the precursor cells for the mechanosensory lateral line system. XKrk1 is the first reported marker for lateral line stem cells.
 ...
PMID:A Xenopus c-kit-related receptor tyrosine kinase expressed in migrating stem cells of the lateral line system. 761 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>