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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
1994-5-6
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pubmed:abstractText |
The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play a crucial role in mast cell growth and differentiation. In a human mast cell leukemia cell line (HMC-1), KitR was found to be constitutively phosphorylated on tyrosine, activated and associated with phosphatidylinositol 3-kinase (P13K) in the absence of autocrine production of SCF. Sequencing of c-kit cDNA revealed that c-kit genes of HMC-1 cells were composed of a normal, wild-type allele and a mutant allele with two point mutations in codon 560 and codon 816, resulting in intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp, respectively. Murine c-kit mutants encoding Gly-559 and/or Val-814, corresponding to human Gly-560 and/or Val-816, were constructed by site-directed mutagenesis and expressed in cells of a human embryonic kidney cell line (293T). In the transfected cells, KitR (Gly-559 + Val-814) and KitR (Val-814) were strikingly phosphorylated on tyrosine and activated in the absence of SCF, whereas tyrosine phosphorylation and activation of KitR (Gly-559) or wild-type KitR was modest or little, respectively. These results suggest that constitutive activation of KitR in HMC-1 results from the activating mutations of c-kit gene, and raise the possibility that the activating mutations, particularly at codon 814 of murine c-kit or at codon 816 of human c-kit, may participate in oncogenesis of mast cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-kit,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Colony-Stimulating Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0887-6924
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
8 Suppl 1
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pubmed:geneSymbol |
c-kit
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
S18-22
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7512180-Humans,
pubmed-meshheading:7512180-Leukemia, Mast-Cell,
pubmed-meshheading:7512180-Mutation,
pubmed-meshheading:7512180-Proto-Oncogene Proteins,
pubmed-meshheading:7512180-Proto-Oncogene Proteins c-kit,
pubmed-meshheading:7512180-Proto-Oncogenes,
pubmed-meshheading:7512180-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:7512180-Receptors, Colony-Stimulating Factor,
pubmed-meshheading:7512180-Tumor Cells, Cultured
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pubmed:year |
1994
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pubmed:articleTitle |
Activating mutations of the c-kit proto-oncogene in a human mast cell leukemia cell line.
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pubmed:affiliation |
Department of Internal Medicine II, Osaka University Medical School, Suita, Japan.
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pubmed:publicationType |
Journal Article
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