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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

c-fms and c-kit are structurally related tyrosine kinase receptors for colony-stimulating factor-1 (CSF-1) and for steel factor (SF), respectively. The level of c-fms mRNA, like c-kit mRNA, increases during the maturation of oocytes and is an abundant maternal message found in the unfertilized oocyte. Following fertilization, the level of both c-fms and c-kit oocyte mRNAs decreases rapidly until they are no longer detected by the early 2-cell stage. By the late 2-cell stage, both mRNAs are reexpressed, albeit at low levels. This low level of mRNA expression continues throughout preimplantation development. CSF-1 and SF transcripts are not detected in early preimplantation embryos, but are detected in cumulus cells, oviduct, and uterus, suggesting a paracrine action of these growth factors during the preimplantation period. The patterns of CSF-1/c-fms mRNA and SF/c-kit mRNA expression are consistent with the hypothesis that these two ligand/receptor systems may act in a compensatory or synergistic manner during preimplantation development.
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PMID:Expression of CSF-1/c-fms and SF/c-kit mRNA during preimplantation mouse development. 137 50

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor and is shown to be allelic with the white-spotting locus (W) of the mouse. In order to elucidate the role of c-kit protein during placental development, we have examined the expression of c-kit protein in the uterus and placenta of mice at pre- and post-implantation stages by the avidin-biotin-peroxidase (ABC) method using rat anti-mouse c-kit monoclonal antibody. At Days 3 and 5 of pregnancy and pseudo-pregnancy, c-kit protein was detected in the glandular epithelium, but little expression was observed in the luminal epithelium. At Day 7 of pregnancy, expression was detected in the stromal cells around the uterine crypts of the mesometrial portion, but not in the vigorously proliferating decidual cells around the developing embryo. At Days 9 and 10 of pregnancy, the decidua basalis facing invading trophoblasts gradually expressed c-kit protein. In the mature placenta, c-kit protein was detected in the labyrinthine and decidual layers, but in neither the giant trophoblastic nor the spongiotrophoblastic layer. By Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), c-kit mRNA was detected at the stages of periimplantation and placental development. These results suggested that the c-kit protein might be involved in the proliferation and differentiation of placenta.
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PMID:Expression of c-kit protein during placental development. 138 31

The c-kit proto-oncogene encodes a tyrosine kinase receptor and is allelic with the dominant white-spotting (W) locus of the mouse. In this study we investigated the expression of human c-kit protein in various adult and fetal human tissues immunohistochemically using anti-human c-kit monoclonal antibody. To discriminate c-kit+ cells from mast cells expressing c-kit, mast cells were identified by staining with Toluidine blue. In oogonia, spermatogonia and skin melanocytes of the fetus and in oocytes of adult ovary, c-kit expression was detected. In adult uterus, c-kit+ cells were widely distributed in the basal layer of the endometrium, myometrium and cervix, the number and distribution being almost identical to those of mast cells. In fetal uterus, c-kit+ non-mast cells clustered beneath the epithelium and a few mast cells were observed in the myometrium and subserosal layer. In both adult and fetus, c-kit+ non-mast cells were detected within smooth muscle layers of the intestine, colon and oesophagus, while mast cells were observed in the mucosal and submucosal layers of these organs. In contrast to mice, no expression of c-kit protein was detected in the human placenta and decidua. Thus, the distribution of c-kit+ cells in various tissues is similar but not identical between adult and fetus and between human and mouse.
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PMID:The expression of c-kit protein in human adult and fetal tissues. 750 33

Stem cell factor (SCF), or c-kit ligand, is a multipotent growth factor that has been implicated in an important role in various aspects of animal development, including maintenance of the viability of primordial germ cells. A porcine SCF (pSCF) cDNA was generated from porcine uterine endometrial mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR), and its nucleotide sequence was determined. The 952-bp pSCF cDNA contained an open reading frame encoding 274 amino acids. The deduced amino acid sequence of pSCF is approximately 86%, 83%, and 82%, identical to human, rat, and mouse SCFs, respectively; and it contains the four conserved cysteine residues and Asn-linked glycosylation sites. One additional amino acid was identified in pSCF, Glu130, which is not in the human (hSCF), rat (rSCF), or mouse (mSCF) sequences. Northern analysis of poly(A)+ RNA obtained from Day 16 pregnant endometrium revealed a transcript of approximately 6.5 kb. The size of this transcript is consistent with the size of full-length SCF mRNA, and the occurrence of alternatively spliced pSCF mRNAs were not detected by RT-PCR/Southern hybridization analysis of endometrial and ovarian total cellular RNA (tcRNA). Porcine SCF mRNA has been localized by in situ hybridization in porcine endometrial stromal tissue. Pregnancy does not appear to be a prerequisite for pSCF mRNA expression in endometrial tissue since it was detectable in tissue and tcRNA obtained from pregnant and nonpregnant gilts. The biological significance of uterine pSCF expression is currently unclear, but it probably participates in intracellular communication within the uterus.
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PMID:Porcine stem cell factor/c-kit ligand: its molecular cloning and localization within the uterus. 750 58

Mutations at either W or mi (microphthalmia) loci in the mouse can lead to a deficiency in melanocytes and mast cells. In addition, W mutants can be anemic and sterile, whereas mi mice are osteopetrotic because of a monocyte/macrophage/osteoclast defect. Since c-kit receptor tyrosine kinase is the gene product of the W locus and mi mutation has been suggested to affect the transduction of signals from the c-kit and c-fms receptors, we here examined the effect of mi mutation on fertility. Testes and ovaries from mi/mi mice were histologically normal, and the pattern of c-kit protein expression was not different from that of +/+ mice. Homozygous mutant crosses (mi/mi x mi/mi) were fertile, but inversion of the uterus occurred in 86% of the deliveries. In some cases, the placenta was found still attached to the inverted uterus after delivery. Decidual cells were present and expressed c-kit protein normally in the placenta of mi/mi mice. The inversion was also observed in mi/mi females mated to +/+ males. No uterine inversion was noted when +/mi females were crossed with mi/mi or +/mi males, suggesting that the genotype of the mother but not of the father or fetus is important for the pathogenesis. The numbers and body weights of mi/mi newborns were less than those of +/mi littermates. Mast cells were absent, but c-kit-positive cells were present, in the uterine muscle layers of pregnant mi/mi mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High incidence of uterine inversion in mast cell-deficient osteopetrotic mutant mice of mi/mi genotype. 751 99

The c-kit receptor and its cognate ligand, KL, play a critical role in melanogenesis, gametogenesis, and hematopoiesis. Studies on the expression of c-kit and KL have been primarily focused on mouse development. We undertook the present study to characterize the pattern of expression of these molecules in normal adult human tissues. Using immunohistochemistry and consecutive tissue sections from the same block, we evaluated a variety of well-preserved normal tissues for c-kit and KL microanatomic distribution. c-kit protein was identified in tissue mast cells, melanocytes, glandular epithelial cells of breast, parotid, dermal sweat, and esophageal glands. Scattered c-kit immunoreactivity was also observed for testicular and ovarian interstitial cells. A striking regional distribution of c-kit was detected in the central nervous system, particularly in the cerebellum, hippocampus, and dorsal horn of the spinal cord. KL protein was identified in cells complementary to staining for the receptor, such as glandular myoepithelium of breast and sweat glands. Intense KL immunoreactivity was observed in smooth muscle cells of the bladder, cervix, uterus, and gastrointestinal tract, as well as in striated and cardiac muscle. Strong KL staining was also detected in prostate fibromuscular stroma cells. In the central nervous system, KL expression was confined to Golgi and Purkinje cells in the cerebellum. These results suggest a role for this receptor and its ligand in the maintenance of a variety of fully differentiated tissues.
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PMID:Expression of c-kit and kit ligand proteins in normal human tissues. 752 89

Basophils and mast cells represent distinct cell lineages within the hemopoietic system. Based on the unique cell surface antigen profile of both cells, we have established methods which allow the reproducible purification to homogeneity (> 99%) of normal human basophil granulocytes from the peripheral blood and of mast cells from human dispersed tissues. Basophils (n = 9) were purified by current counterflow elutriation followed by depletion of monocytes with CD14 mAb conjugated to magnetic beads, and subsequent cell sorting for CD217+ cells. Basophil purity was 99.5 +/- 0.4% (range 98.7-99.9%). Mast cells were obtained from lung (n = 6), uterus (n = 1), mastocytosis bone marrow (n = 2), and human foreskin (n = 2). Mast cells were purified by collagenase digestion followed by current counterflow elutriation and sorting with CD117/c-kit mAb. Mast cell purity was 99.4 +/- 0.7% (range: 97.5-99.9%). Purified cells were more than 90% viable and were able to release histamine on induction with IgE plus anti-IgE. Furthermore, the PCR technique could be applied on pure cells and confirmed expression of high affinity IgE receptor (Fc epsilon R1) alpha chain mRNA. Thus, by combining isolation techniques including elutriation, magnetic cell depletion and cell sorting with mAb, functionally intact normal human basophils and mast cells can be enriched to homogeneity.
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PMID:Purification of human basophils and mast cells by multistep separation technique and mAb to CDw17 and CD117/c-kit. 753 67

Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 micrograms/ml: 26.9 +/- 3.4%; other chemokines: < 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (< 1 microgram/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n = 2), skin (n = 1), uterus (n = 3), or tonsils (n = 3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2R beta, CD63, IL-3R alpha, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.
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PMID:Differential response of human basophils and mast cells to recombinant chemokines. 754 Dec 56

Recent data suggest that stem cell factor (SCF or c-kit ligand, KL) is a major regulator of human mast cells (MCs). In the present study, MCs derived from the lung (n = 8), uterus (n = 14) and heart (n = 4) were analyzed for expression of c-kit receptor and for responses to recombinant SCF. MCs of all organs tested were recognized by mAbs to c-kit (YB5.B8, SR-1) as assessed by combined toluidine blue/immunofluorescence staining. Activation by rhSCF (10 ng/ml, 60 min) resulted in histamine release from lung MCs (SCF 12.8 +/- 2.7% histamine release; control 2.8 +/- 0.8%, p < 0.01), uterus MCs (SCF 16.8 +/- 5.8%; control 5.2 +/- 2.5%, p < 0.01) and heart MCs (SCF 18.4 +/- 2.6%; control 1.7 +/- 0.23%, p < 0.01). Short-term pre-incubation with rhSCF (15 min) did not result in histamine secretion (p > 0.05), but in an increase (lung 2.4 +/- 1.0 fold; uterus 2.1 +/- 1.1 fold, and heart 2.0 +/- 0.4 fold) of alpha IgE-induced mediator release (p < 0.05). The effects of SCF were dose-dependent (maximum responses at 10-100 ng/ml) and dependent on extracellular calcium. A monoclonal antibody to SCF was found to inhibit the effects of SCF on MCs. Furthermore, MCs could be desensitized specifically by pre-incubation of MCs with rhSCF in Ca-free medium. Together, these data suggest that SCF triggers mediator secretion from MCs in various organs via binding to the c-kit receptor.
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PMID:Specific activation of human mast cells by the ligand for c-kit: comparison between lung, uterus and heart mast cells. 769

Mast cells (MC) are proinflammatory immune cells residing in various organs. Tissue-specific heterogeneity of MC has been described. The aim of this study was to establish the phenotype and functional profile of human tonsillar mast cells (ToMC) and to compare ToMC with lung-, skin-, and uterus MC. Tonsillar tissue was obtained from 23 patients suffering from hyperplastic tonsils and dispersed by enzymatic digestion. With the use of a combined toluidine blue/immunofluorescence staining technique, isolated ToMC were found to react with monoclonal antibodies (mAb) to immunoglobulin E, CD9, CD43, CD44, CD46, CD54, CD55, and CD59, as well as mAb to stem cell factor (SCF) receptor (CD117/c-kit). ToMC were not recognized by mAb to other cytokine receptors or mAb to CD3, CD11b, CD14, CDw17, the skin MC marker CD88 (C5aR) or CD89 (Fc alphaR). Activation of ToMC by recombinant human (rh) SCF or anti-IgE resulted in histamine secretion, whereas no effects were seen with rhC5a, rh granulocyte-macrophage colony-stimulating factor, or rh interleukin-1 through -10. In summary, ToMC exhibit functional and phenotypic properties similar to lung- or uterus MC. Unlike skin MC, ToMC lack C5aR and are unresponsive to rhC5a.
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PMID:Immunophenotypic and functional characterization of human tonsillar mast cells. 912 8


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