| First Author | Tsujimura T | Year | 1994 |
| Journal | Blood | Volume | 83 |
| Issue | 9 | Pages | 2619-26 |
| PubMed ID | 7513208 | Mgi Jnum | J:17895 |
| Mgi Id | MGI:65918 | Doi | 10.1182/blood.v83.9.2619.2619 |
| Citation | Tsujimura T, et al. (1994) Ligand-independent activation of c-kit receptor tyrosine kinase in a murine mastocytoma cell line P-815 generated by a point mutation. Blood 83(9):2619-26 |
| abstractText | The c-kit proto-oncogene encodes a receptor tyrosine kinase that is known to play a crucial role in hematopoiesis, especially in mast cell growth and differentiation. Although a number of dominant loss-of-function mutations of c-kit gene have been well characterized in mice, rats, and humans, little is known about the c-kit mutations contributing to ligand-independent activation of the c-kit receptor tyrosine kinase (KIT). In a murine mastocytoma cell line, P-815, KIT has been found to be constitutively phosphorylated on tyrosine and activated in a ligand-independent manner. Sequencing of the whole coding region of c-kit cDNA showed that c-kit cDNA of P-815 cells carries a point mutation in codon 814, resulting in amino acid substitution of Tyr for Asp. Murine wild-type c-kit cDNA and mutant-type c-kit cDNA encoding Tyr in codon 814 were expressed in cells of a human embryonic kidney cell line, 293T. In the transfected cells, mutant-form KITTyr814 was strikingly phosphorylated on tyrosine and activated in immune complex kinase reaction regardless of stimulation with a ligand for KIT (stem cell factor), whereas tyrosine phosphorylation and activation was barely detectable in wild-form KIT. The data presented here provide evidence for a novel activating mutation of c-kit gene that might be involved in neoplastic growth or oncogenesis of some cell types, including mast cells. |
