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

We have cloned and sequenced the human KIT proto-oncogene, which contains 21 exons and spans more than 34 kb of DNA on chromosome segment 4q12. We also establish physical linkage between the KIT gene and the related PDGFRA gene. The organization of the KIT gene is virtually identical to that of the homologous FMS gene, located on chromosome 5. Together, these data suggest that the KIT and PDGFRA genes on chromosome 4 and the FMS and PDGFRB genes on chromosome 5 arose by duplication of a common ancestral gene, followed by duplication of a chromosome.
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PMID:Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene. 127 99

The recent identification of the mouse White spotting and Steel loci as genes encoding the c-kit receptor and its ligand, respectively, has shed light on the importance of this ligand and receptor in embryogenesis, melanogenesis and hematopoiesis. In order to determine if the c-kit proto-oncogene is involved in human disease, we isolated seven overlapping lambda recombinants, using a fetal brain cDNA, and characterized the normal human gene (KIT). The longest mapped transcript is 5230 bp, is alternatively spliced and includes 21 exons that span more than 70 kb of DNA. From the exon-intron structure, we have localized an alternative splice site to the 3' end of exon 9. The overall c-kit gene structure closely resembles that found in the CSF-1R gene (c-fms). This similarity includes a large first intron, the same number of exons containing translated sequence and very similar exon-intron boundaries. Using pulsed-field gel electrophoresis, we have linked KIT to the platelet-derived growth factor receptor A gene, with both residing on a 700-kb BssHI fragment. These data will allow investigation into the control of KIT expression and the potential to identify mutations or altered expression of this gene in human disease.
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PMID:Cloning and structural analysis of the human c-kit gene. 137 10

Piebaldism is a rare autosomal dominant disorder of pigmentation, characterized by congenital patches of white skin and hair from which melanocytes are absent. We have previously shown that piebaldism can result from missense and frameshift mutations of the KIT proto-oncogene, which encodes the cellular receptor tyrosine kinase for the mast/stem cell growth factor. Here, we report two novel KIT mutations associated with human piebaldism. A proximal frameshift is associated with a mild piebald phenotype, and a splice-junction mutation is associated with a highly variable piebald phenotype. We discuss the apparent relationship between the predicted impact of specific KIT mutations on total KIT-dependent signal transduction and the severity of the resultant piebald phenotypes.
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PMID:Mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene account for a continuous range of phenotypes in human piebaldism. 138 25

The c-kit proto-oncogene, the gene at the mouse W developmental locus, is one of a substantial group of genes that appear to encode cell surface receptors but for which the ligands are unknown. We have characterized the kit ligand by a generally applicable approach: the receptor extracellular domain was genetically fused to placental alkaline phosphatase, producing a soluble receptor affinity reagent with an enzyme tag that could be easily and sensitively traced. This fusion protein, APtag-KIT, was used to demonstrate a specific binding interaction (KD = 3 x 10(-8) M) with a ligand on 3T3 fibroblast lines. In situ staining showed labeling over the whole surface of the 3T3 cells, but not extending to adjacent nonexpressing cells. These findings provide direct molecular evidence that the kit ligand can exist as a cell surface protein. Binding was not detected on 3T3 fibroblasts carrying the steel (Sl) mutation, confirming the biological significance of the binding activity and demonstrating that mutations at the Sl locus affect the expression or structure of the kit ligand.
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PMID:The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. 169 55

The full-length cDNA of the receptor for human AA-type platelet-derived growth factor (PDGF) was used to assign the PDGFRA gene to region q11----q21 of human chromosome 4 and to mouse Chromosome 5 by somatic cell hybrid analysis. Since the same region also contains the c-kit oncogene homolog KIT, we carried out pulsed-field gel electrophoresis to determine the physical distance between the two genes in human DNA. The two probes, when successively applied to the same filters, hybridized to a 450-kb EagI-fragment but not to other common restriction fragments. The genes are separated by at least one NotI, one XhoI, and one SalI site.
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PMID:Chromosomal localization of the gene for AA-type platelet-derived growth factor receptor (PDGFRA) in humans and mice. 171 35

In order to characterise the distribution and role of stem cell factor (SCF), a recently-reported growth factor for normal melanocytes, we carried out an immunohistochemical study on benign and malignant melanocytic tumours with a comparison with the presence of its receptor c-Kit proto-oncogene product (c-KIT). In normal skin, SCF was mainly observed in endothelial cells of blood vessels but not frequently in basal melanocytes, whereas c-KIT was predominantly localised in tissue mast cells. In benign neoplastic melanocytes (common melanocytic naevi), localisation of SCF and c-KIT was complementary: SCF was mostly found in dermal naevus cells while c-KIT was revealed in epidermal naevus cells, although the expression of the latter antigen was not frequent. Malignant melanoma cells showed less frequent expression of these antigens than those in benign lesions. Of five cultured melanoma cell lines, SCF was observed in only one, and c-KIT was not found in any melanoma cells. No quantitative or qualitative alterations assessed by Western blot analysis were induced in the presence of phenotypic modifiers (sodium butyrate and HMBA). Present data suggest that loss of SCF expression in neoplastic melanocytes is commonly associated with malignant transformation of pigment cells rather than loss of its receptor c-KIT.
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PMID:Immunohistochemical localisation of stem cell factor (SCF) with comparison of its receptor c-Kit proto-oncogene product (c-KIT) in melanocytic tumours. 749 98

Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Piebaldism results from mutations of the KIT proto-oncogene, which encodes the cell-surface receptor transmembrane tyrosine kinase for an embryonic growth factor, Steel factor. Several pathologic mutations of the KIT gene have now been identified in different patients with piebaldism. Correlation of these mutations with the associated piebald phenotypes has led to the recognition of a hierarchy of three classes of mutations that result in a graded series of piebald phenotypes, and to improved understanding of the mechanisms that underlie dominant genetic disorders.
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PMID:Molecular basis of human piebaldism. 752 36

We examined the expression of Fc epsilon-RI and Fc gamma-RII/III on mouse bone marrow cells enriched for hematopoietic progenitors including mast cell progenitors. Bone marrow cells were depleted of mature hematopoietic lineages and a primitive population of cells that express the proto-oncogene c-kit (KIT+ lineage- cells) was isolated. KIT+ lineage- cells stain positively using the Ab 2.4G2, indicating surface expression of Fc gamma-RII and/or Fc gamma-RIII. Fluorescent staining of intracytoplasmic domains of Fc gamma-RII and Fc gamma-RIII revealed that these cells express primarily Fc gamma-RII on their surface. KIT+ lineage- cells did express Fc gamma RIII alpha-chain protein, but predominately in the nuclear/perinuclear area. We could not detect surface expression of Fc epsilon-RI by KIT+ lineage- cells, although a heterogeneous population of KIT- cells does bind IgE with high affinity and may reflect cells of the basophilic lineage. KIT+ lineage- cells cultured with SCF and IL-3 generate numerous mast cells, whereas equivalent numbers of KIT- cells or naive bone marrow cells do not. In these cultures, surface expression of Fc epsilon-RI is detected on a small number of cells by day 3 of culture with increased surface expression levels correlating roughly with metachromatic granule formation. The fact that Fc gamma-RIII and Fc epsilon-RI are not expressed on the cell surface of KIT+ lineage- cells but appear later in hematopoietic development makes it unlikely that these receptors influence early hematopoietic differentiation. The role that might justify such a complete surface expression of Fc gamma-RII by bone marrow progenitors remains to be identified.
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PMID:Murine KIT+ lineage- bone marrow progenitors express Fc gamma-RII but do not express Fc epsilon-RI until mast cell granule formation. 752 15

Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Piebaldism results from mutations of the KIT proto-oncogene, which encodes the cellular receptor transmembrane tyrosine kinase for mast/stem cell growth factor. Here we describe two novel KIT mutations associated with human piebaldism. These amino acid substitutions, located in the most highly conserved sections of the KIT kinase domain, would be expected to dominant-negatively inhibit KIT-dependent signal transduction, resulting in aberrant melanocyte proliferation or migration during embryologic development.
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PMID:Novel mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. 768 67

Previous studies in vivo and in vitro show that KIT kinase promotes normal melanocyte development and growth. However, the role of the KIT proto-oncogene in neoplastic melanocytes is not certain. We therefore examined KIT expression and function in human melanomas. Our results show that KIT mRNA was expressed in 12 of 28 melanoma cell lines (approximately 40%), mainly in those originating from pigmented tumors. Surprisingly, activation of KIT with mast cell growth factor (MGF) in melanoma cells produced biological responses opposite to those elicited in normal melanocytes. MGF inhibited rather than stimulated the growth of metastatic melanoma cell lines. The opposite effects may be due to aberrant signal transduction by KIT in melanoma cells in response to MGF. The in vitro inhibition of melanoma cells by MGF suggests that growth in vivo of this tumor is not promoted by KIT kinase activation, but rather that transformed melanocytes might regress when MGF is expressed in their immediate environment.
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PMID:KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells. 768 62


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