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

Recent reports have shown that various marrow-derived cell populations respond vigorously to recombinant rat stem cell factor (rrSCF164), one form of the kit-ligand. In the present study, we isolated cell populations from rat bone marrow using the Thy 1.1 antigen (an antigen that in the rat is differentially expressed on primitive hemopoietic progenitor cells) and fluorescently conjugated rrSCF164 (rrSCF164-PE). We show that rrSCF164 only stimulates cells that are enriched in the brightest Thy 1.1 populations (Thy 1.1bright). Numerous cell lines were generated by serial passage in rrSCF164 containing medium, and the prototypic cell lines have been designated SRT002 and SRT003. Each cell line retains the Thy 1.1bright phenotype and does not respond to interleukins (IL) 1-8, IL-10, granulocyte (G) colony-stimulating factor (CSF), granulocyte macrophage (GM) CSF, M-CSF, or crude preparations of mitogen-stimulated T-cell supernatants. The Thy 1.1bright population of rat marrow was subdivided into a subset that binds rrSCF164-PE (Thy 1.1bright, rrSCF164+). The majority of these cells possess certain characteristics in common with marrow-derived mast cells and the Thy 1.1bright, rrSCF164 responsive cell lines, having similar granule morphology, being metachromatic, and reacting positively with alcian blue. Moreover, rats treated with rrSCF164 displayed significant increases in Thy 1.1bright, rrSCF164+ cells in the bone marrow. These studies show that the combination of Thy 1.1 and rrSCF164 makes possible the isolation of a unique subset of rat bone marrow cells that differentially express the Thy 1.1 antigen and the cell surface receptor c-kit, the majority of which are morphologically similar to marrow-derived mast cells.
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PMID:Isolation of rat bone marrow mast lineage cells using Thy 1.1 and rat stem cell factor. 128 Feb 77

The proto-oncogene c-Kit, a transmembrane receptor tyrosine kinase, is an important regulator of cell growth whose constitutively active oncogenic counterpart, v-kit, induces sarcomas in cats. Mutations in murine c-kit that reduce the receptor tyrosine kinase activity cause deficiencies in the migration and proliferation of melanoblasts, hematopoietic stem cells, and primordial germ cells. We therefore investigated whether c-Kit regulates normal human melanocyte proliferation and plays a role in melanomas. We show that normal human melanocytes respond to mast cell growth factor (MGF), the Kit-ligand that stimulates phosphorylation of tyrosyl residues in c-Kit and induces sequential phosphorylation of tyrosyl residues in several other proteins. One of the phosphorylated intermediates in the signal transduction pathway was identified as an early response kinase (mitogen-activated protein [MAP] kinase). Dephosphorylation of a prominent 180-kDa protein suggests that MGF also activates a phosphotyrosine phosphatase. In contrast, MGF did not induce proliferation, the cascade of protein phosphorylations, or MAP kinase activation in the majority of cells cultured from primary nodular and metastatic melanomas that grow independently of exogenous factors. In the five out of eight human melanoma lines expressing c-kit mRNAs, c-Kit was not constitutively activated. Therefore, although c-Kit-kinase is a potent growth regulator of normal human melanocytes, its activity is not positively associated with malignant transformation.
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PMID:c-Kit-kinase induces a cascade of protein tyrosine phosphorylation in normal human melanocytes in response to mast cell growth factor and stimulates mitogen-activated protein kinase but is down-regulated in melanomas. 137 24

Studies from several laboratories have provided evidence that distinct stromal cell-derived signals are involved in the maturation of pre-B cells into surface Ig expressing B lymphocytes. In order to define the stage of development at which these stimuli act, various polymerase chain reaction strategies were used to characterize the status of kappa L chain gene rearrangements in nontransformed, stromal cell dependent pre-B cells. These cells were obtained from lymphoid colonies whose growth was potentiated by factors from a stromal cell line. kappa L chain genes in cells from many of these colonies were rearranged, and analysis of the Jk genes used indicated a bias toward the most 3' loci. However, the use of a reverse transcriptase PCR strategy failed to detect mature kappa transcripts, indicating that stromal cell mediators exist that allow pre-B cells to progress to the stage at which L chain genes are rearranged but not expressed. Reverse transcriptase PCR further revealed that no transcripts for c-kit (the receptor for kit-ligand) and the IL-7R could be detected in these cells. This suggests that these receptors are no longer expressed by the time cells have undergone kappa rearrangements and minimize a role for stromal cell-derived kit-ligand and IL-7 in mediating the pre-B to B cell transition.
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PMID:Status of kappa L chain gene rearrangements and c-kit and IL-7 receptor expression in stromal cell-dependent pre-B cells. 138 91

Kit-ligand is a novel polypeptide growth factor which binds and activates the c-kit protooncogene, a receptor tyrosine kinase. We used the technique of reverse transcription-polymerase chain reaction to demonstrate the expression of this growth factor in human placenta. In situ hybridization showed that kit-ligand mRNA is expressed in cytotrophoblast and syncytiotrophoblast cells in the placenta, and in fetally derived extravillous trophoblast cells which have invaded the maternal endometrium. Five species of mRNA encoding variants of kit-ligand were identified by nested reverse transcription-polymerase chain reaction. Cloning and sequencing indicate that these variants arise by alternative splicing of the kit-ligand transcript. One of these species, KL486, uses a novel splice site in exon 8. There is a different pattern of expression of the variants in amnion, chorion, trophoblast, and placenta, indicating tissue-specific control of splicing.
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PMID:Expression of messenger RNA for kit-ligand in human placenta: localization by in situ hybridization and identification of alternatively spliced variants. 138 93

The regenerative potential of bone marrow following exposure to relatively high doses of ionizing radiation, as well as the efficacy of hemopoietic growth factor treatment, are dependent on the residual number of hemopoietic stem cells. From studies in mice in particular, evidence has been obtained that immature hemopoietic stem cells are heterogenous with respect to repopulating capacity, with one subset being capable of short-term, transient hemopoietic reconstitution and another subset of sustained reconstitution. In rhesus monkeys, CD34+, RhLA-DRdull cells were identified as the small fraction of a bone marrow cell that contains reconstituting hemopoietic stem cells. The growth factor receptor phenotype of this immature cell fraction has been determined for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and IL-6 as well as for kit-ligand, making c-kit an especially strong growth factor receptor marker for reconstituting stem cells. In addition, it is demonstrated that CD34+ cells appear in peripheral blood after exposure to radiation and are correlated to numbers of CD34+ cells in bone marrow. This finding suggests that circulating CD34+ cells may be used as a cellular marker with prognostic significance for both the number of residual stem cells as well as regeneration of immature hemopoietic cells in bone marrow.
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PMID:Surface markers and growth factor receptors of immature hemopoietic stem cell subsets. 748 42

The c-kit receptor tyrosine kinase belongs to the PDGF/CSF-1/c-kit receptor subfamily. The kit-ligand, KL, also called steel factor, is synthesized from two alternatively spliced mRNAs as transmembrane proteins that can either be proteolytically cleaved to produce soluble forms of KL or can function as cell-associated molecules. The c-kit receptor kinase and KL are encoded at the white spotting (W) and steel (Sl) loci of the mouse, respectively. Mutations at both the W and the Sl locus cause deficiencies in gametogenesis, melanogenesis and hematopoiesis. The c-kit receptor is expressed in the cellular targets of W and Sl mutations, while KL is expressed in their microenvironment. In melanogenesis, c-kit is expressed in melanoblasts from the time they leave the neural crest and expression continues during embryonic development and in the melanocytes of postnatal animals. In gametogenesis c-kit is expressed in primordial germ cells, in spermatogonia, and in primordial and growing oocytes, implying a role at three distinct stages of gametogenesis. Many mutant alleles are known at W and Sl loci and their phenotypes vary in the degree of severity in the different cellular targets of the mutations. While many W and Sl alleles severely affect primordial germ cells (PGC), several mild Sl alleles have weak effects on PGCs and exhibit differential male or female sterility. Steel Panda (Sl(pan)) is a KL expression mutation in which KL RNA transcript levels are reduced in most tissues analyzed. In female Sl(pan)/Sl(pan) mice, ovarian follicle development is arrested at the one layered cuboidal stage as a result of reduced KL expression in follicle cells, indicating a role for c-kit in oocyte growth. Wsh is a c-kit expression mutation, which affects mast cells and melanogenesis. While the mast cell defect results from lack of c-kit expression, the pigmentation deficiency appears to stem from ectopic c-kit receptor expression in the somitic dermatome at the time of migration of melanoblasts from the neural crest to the periphery. It is proposed that the ectopic c-kit expression in Wsh mice affects early melanogenesis in a dominant fashion. The "sash" or white belt of Wsh/+ animals and some other mutant mice is explained by the varying density of melanoblasts along the body axis of wild-type embryos.
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PMID:The kit-ligand (steel factor) and its receptor c-kit/W: pleiotropic roles in gametogenesis and melanogenesis. 751 81

Mechanisms affecting mast cell and melanocyte growth and function are still poorly understood. This report summarizes the current state of knowledge on a recently described growth factor for both these cell types and for primitive haematopoietic stem cells. Stem cell factor (SCF), also named mast cell growth factor or kit-ligand, has only recently been cloned and has been shown to be encoded on human chromosome 12. It may be of specific importance in cutaneous physiology and pathology since it is produced by several cell types in the skin (e.g. fibroblasts, keratinocytes, endothelial cells) and since it affects melanocyte and mast cell growth, survival, secretion and adhesion as well as migration into tissues. Defects in the genes encoding for the SCF receptor (c-kit-protein) have been shown to be responsible for human piebaldism. A pathogenetic role in mastocytosis has recently been proposed, but remains to be proven. SCF receptor expression is decreased on cells of some malignant cell lines compared to their physiological counterparts, making it unlikely that SCF is a key factor in malignant transformation and cellular hyperproliferation. In haematopoiesis, SCF acts primarily in concert with other growth factors, and we show here that alone in serum-free culture it has no effect on mast cell growth. Furthermore, there is evidence that besides SCF, additional mast cell growth factors are secreted by fibroblasts and keratinocytes, suggesting a complex orchestration of several growth factors in the regulation of cutaneous growth and differentiation in which SCF plays only one part.
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PMID:Stem cell factor, a novel cutaneous growth factor for mast cells and melanocytes. 753 33

After more than a decade since Whitlock and Witte established an in-vitro long-term culture of bone marrow B lineage cells, c-kit+IL-7-receptor(R)+B precursor cells in fresh bone marrow are now able to be grown under a fully defined culture condition containing only BSA, transferrin, IL-7 and the ligand for c-kit(Kit-ligand;KL) as protein components. On the other hand, previous studies indicated that the actual intramarrow B-cell-genesis is a complex process involving multiple stromal cell-derived molecules. Thus, the next step for the culture of B-cell genesis is to develop this simple culture into a new defined culture of B-cell-genesis that is closer to the actual process. In this article, we will describe how this defined culture condition has developed from the original Whitlock-Witte type culture, how the B precursors under this culture-condition are different from that in the bone marrow, and finally our biased view on the future direction to which this defined culture should develop.
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PMID:Making the in-vitro model closer to actual B lymphopoiesis in the bone marrow. 757 5

Sorted fractions from mouse bone marrow containing highly purified hemopoietic stem and progenitor cells were studied for the expression of growth factor receptors. With the use of rhodamine 123 WGA+, 15-1.1-, low density cells were separated into quiescent pluripotent stem cells and committed progenitor cells. RNA was extracted and cDNA was prepared by reverse transcription. Using primers specific for growth factor receptors, the cDNA of each sorted fraction was amplified by polymerase chain reaction (PCR). The quiescent rhodamine 123 dull stem cell fraction was found to express the interleukin 3 (IL-3) receptor beta unit and c-kit, but not the granulocyte-macrophage colony stimulating factor (GM-CSF) receptor beta unit nor flk-2. The rhodamine 123 bright fraction with activated stem cells and mostly committed progenitor cells similarly expressed the IL-3-R beta, and c-kit. However, this fraction also expressed flk-2 and GM-CSF-R beta. Since the expression of c-kit in the stem cell fraction does not correspond with the poor response to the kit-ligand stem cell factor (SCF) by these cells, we further analyzed the fractions with respect to their binding of biotinylated SCF. The SCF-binding cells were found to be all rhodamine 123 bright. This indicates that the expression of c-kit is not sufficient to yield a functional receptor for SCF; c-kit probably needs a partner molecule to form a functional high-affinity binding site for SCF. Similar to the beta unit of the GM-CSF receptor, this partner is then not expressed in the stem cell fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The expression of cytokine receptors by purified hemopoietic stem cells. 769 28

In the mouse testis, spontaneous death of spermatogonia has a large impact on the output of differentiating spermatids. The tyrosine kinase receptor c-kit is expressed in type A, intermediate, and B spermatogonia, and kit-ligand (KL) is expressed in Sertoli cells. Previous work indicated a depletion of type A spermatogonia after in vivo exposure to an antibody that blocks c-kit function. The present work was undertaken to determine whether blocking c-kit function results in apoptosis of spermatogonia or in an inability of spermatogonia to proliferate. Testes sections were stained by a method that detects apoptotic cells in situ. In testes of 8-day postnatal (P8) males, type A spermatogonia are the predominant germ cell type present. Stained sections from P8 males injected with the c-kit antagonistic antibody ACK2 showed a fivefold higher rate of cell death than uninjected controls. At least a twofold increase was observed in P12 and P30 injected males and in P30 SId/+ males as compared to uninjected controls. Determination of the stage of germ cell development that was affected in P30 males indicated that the frequency of gonial cell death was increased fourfold, but the frequency of death in spermatocytes around the time of the meiotic division was increased 15-fold. It is concluded that KL acts to prevent apoptosis in the testis in vivo, that the membrane bound form of KL may be more effective, and that survival of late meiotic and dividing spermatocytes is regulated by KL through an indirect mechanism probably mediated by Sertoli cells. Thus, KL is an important regulator of spermatid output.
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PMID:Kit ligand mediates survival of type A spermatogonia and dividing spermatocytes in postnatal mouse testes. 857 44


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