| First Author | Tan JC | Year | 1990 |
| Journal | Science | Volume | 247 |
| Issue | 4939 | Pages | 209-12 |
| PubMed ID | 1688471 | Mgi Jnum | J:10187 |
| Mgi Id | MGI:58642 | Doi | 10.1126/science.1688471 |
| Citation | Tan JC, et al. (1990) The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase. Science 247(4939):209-12 |
| abstractText | The murine white spotting locus (W) is allelic with the proto-oncogene c-kit, which encodes a transmembrane tyrosine protein kinase receptor for an unknown ligand. Mutations at the W locus affect various aspects of hematopoiesis and the proliferation and migration of primordial germ cells and melanoblasts during development to varying degrees of severity. The W42 mutation has a particularly severe effect in both the homozygous and the heterozygous states. The molecular basis of the W42 mutation was determined. The c-kit protein products in homozygous mutant mast cells were expressed normally but displayed a defective tyrosine kinase activity in vitro. Nucleotide sequence analysis of mutant complementary DNAs revealed a missense mutation that replaces aspartic acid with asparagine at position 790 in the c-kit protein product. Aspartic acid-790 is a conserved residue in all protein kinases. These results provide an explanation for the dominant nature of the W42 mutation and provide insight into the mechanism of c-kit-mediated signal transduction. |
