Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-5-22
pubmed:abstractText
The c-kit protooncogene encodes a receptor tyrosine kinase that mediates signals required for differentiation, proliferation and survival of mast cells. We have already shown the constitutive activation of c-kit receptor tyrosine kinase (KIT) in a human mast cell leukemia line (HMC-1) and a murine mastocytoma cell line (P-815). We here examined whether such constitutive activation of KIT occurred in the rat tumor mast cell line RBL-2H3 as well, which is frequently used as a tool for studying functions of mast cells. In RBL-2H3 cells, KIT was constitutively phosphorylated on tyrosine and activated in the absence of autocrine production of its ligand, stem cell factor (SCF). Sequencing analysis revealed that one of c-kit genes of RBL-2H3 cells had a point mutation, resulting in amino acid substitution of Tyr for Asp in codon 817. When rat wild-type c-kit cDNA and mutant-type c-kit cDNA encoding KITTyr817 were transfected into cells of a human embryonic kidney cell line (293T), only mutant form KITTyr817 was constitutively phosphorylated on tyrosine and activated in the absence of SCF. Since mutations at the same Asp codon constitutively activated KIT in all the human HMC-1, murine P-815, and rat RBL-2H3 cell lines, and since the incorporation of antisense oligonucleotides of c-kit messenger RNA significantly suppressed the proliferation of RBL-2H3 cells, the activating mutations in the Asp codon of the c-kit gene appeared to be involved in neoplastic growth of mast cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1018-2438
pubmed:author
pubmed:issnType
Print
pubmed:volume
106
pubmed:geneSymbol
c-kit
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
377-85
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:7536501-Amino Acid Sequence, pubmed-meshheading:7536501-Animals, pubmed-meshheading:7536501-Aspartic Acid, pubmed-meshheading:7536501-Base Sequence, pubmed-meshheading:7536501-DNA, Complementary, pubmed-meshheading:7536501-Humans, pubmed-meshheading:7536501-Mice, pubmed-meshheading:7536501-Molecular Sequence Data, pubmed-meshheading:7536501-Mutation, pubmed-meshheading:7536501-Oligonucleotides, Antisense, pubmed-meshheading:7536501-Phosphorylation, pubmed-meshheading:7536501-Proto-Oncogene Proteins, pubmed-meshheading:7536501-Proto-Oncogene Proteins c-kit, pubmed-meshheading:7536501-Rats, pubmed-meshheading:7536501-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:7536501-Receptors, Colony-Stimulating Factor, pubmed-meshheading:7536501-Transfection, pubmed-meshheading:7536501-Tumor Cells, Cultured, pubmed-meshheading:7536501-Tyrosine
pubmed:year
1995
pubmed:articleTitle
Substitution of an aspartic acid results in constitutive activation of c-kit receptor tyrosine kinase in a rat tumor mast cell line RBL-2H3.
pubmed:affiliation
Department of Pathology, Osaka University Medical School, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't