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Constitutive activation of c-kit in FMA3 murine mastocytoma cells caused by deletion of seven amino acids at the juxtamembrane domain
- Source :
- Blood. 87:273-283
- Publication Year :
- 1996
- Publisher :
- American Society of Hematology, 1996.
-
Abstract
- A peculiar point mutation results in constitutive activation of c-kit receptor tyrosine kinase (KIT) in three different tumor mast cell lines; ie, the HMC-1, P-815, and RBL-2H3. Because constitutive activation of KIT was also observed in the FMA3 mouse mastocytoma cell line, we investigated the molecular mechanism. Sequencing of the whole coding region of the c-kit showed that the point mutation found in HMC- 1, P-815, and RBL-2H3 cells was absent in FMA3 cells and that the c-kit cDNA of FMA3 cells carried an in-frame deletion of 21 base pairs (bp) encoding Thr-Gln-Leu-Pro-Tyr-Asp-His at codons 573 to 579 at the juxtamembrane domain. The FMA3-type c-kit cDNA with 21 bp deletion was introduced into the IC-2 cell line, which was derived from murine cultured mast cells. IC-2 cells were dependent on interleukin (IL)-3 and did not express KIT on the surface. In IC-2 cells introduced with the FMA3-type c-kit cDNA, KIT was constitutively phosphorylated on tyrosines and activated. Moreover, the FMA3-type KIT was dimerized without the stimulation by stem cell factor (SCF), a ligand for KIT. The spontaneously dimerized FMA3-type KIT without SCF binding was not internalized even after the activation. IC-2 cells expressing the FMA3- type KIT grew in suspension culture without IL-3 and SCF and became leukemic in nude athymic mice. The deletion of seven amino acids at the juxtamembrane domain appeared to be a new activating mutation of KIT that might be involved in neoplastic growth of mast cells.
- Subjects :
- Molecular Sequence Data
Immunology
Mast-Cell Sarcoma
Mice, Nude
Stem cell factor
Transfection
Biochemistry
Receptor tyrosine kinase
Mice
Species Specificity
Complementary DNA
Proto-Oncogenes
medicine
Tumor Cells, Cultured
Animals
Amino Acid Sequence
Phosphorylation
Peptide sequence
Sequence Deletion
Stem Cell Factor
biology
Base Sequence
Sequence Homology, Amino Acid
Point mutation
Mastocytoma
DNA, Neoplasm
Cell Biology
Hematology
medicine.disease
Molecular biology
Recombinant Proteins
Neoplasm Proteins
Protein Structure, Tertiary
Enzyme Activation
Mice, Inbred C57BL
Proto-Oncogene Proteins c-kit
Cell culture
Vertebrates
biology.protein
Interleukin-3
Protein Processing, Post-Translational
Sequence Alignment
Cell Division
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....6f6eaa786643d98add3a464a582e5d4c