Abstract |
We investigated the mechanism of constitutive activation of c-kit receptor tyrosine kinase (KIT) found in the FMA3 murine mastocytoma cell line, and compared it with the mechanisms observed in other tumor mast cell lines (the HMC-1 human mast cell leukemia cell line, the RBL-2H3 rat mast cell leukemia cell line, and the P-815 murine mastocytoma cell line). The c-kit gene obtained from FMA3 cells was found to have 21-base deletion at the juxtamembrane domain of KIT, thereby leading to the constitutive activation of KIT. The deletion at the juxtamembrane domain resulted in constitutive dimerization of c-kit proteins, whereas the point mutation that were detected at the kinase domain of KIT in HMC-1, RBL-2H3, and P-815 cells caused constitutive activation of KIT without dimerization. These constitutively activating mutations of c-kit may play a role in development of mast cell tumors.
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Authors | T Tsujimura, Y Kanakura, Y Kitamura |
Journal | Leukemia
(Leukemia)
Vol. 11 Suppl 3
Pg. 396-8
(Apr 1997)
ISSN: 0887-6924 [Print] England |
PMID | 9209403
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Proto-Oncogene Proteins c-kit
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Topics |
- Animals
- Dimerization
- Enzyme Activation
- Humans
- Leukemia, Basophilic, Acute
- Leukemia, Mast-Cell
- Mast-Cell Sarcoma
- Mice
- Models, Biological
- Models, Structural
- Point Mutation
- Proto-Oncogene Proteins c-kit
(biosynthesis, chemistry, genetics)
- Rats
- Signal Transduction
- Tumor Cells, Cultured
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