Mechanisms of constitutive activation of c-kit receptor tyrosine kinase.
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.
Tsujimura
T
T
Department of Pathology, Osaka University Medical School, Suita, Japan.
Kanakura
Y
Y
Kitamura
Y
Y
D000818:Animals; D019281:Dimerization; D004789:Enzyme Activation; D006801:Humans; D015471:Leukemia, Basophilic, Acute; D007946:Leukemia, Mast-Cell; D012515:Mast-Cell Sarcoma; D051379:Mice; D008954:Models, Biological; D008961:Models, Structural; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D019009:Proto-Oncogene Proteins c-kit