The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase. Science 1990 Jan 12;247(4939):209-12
Date
01/12/1990Pubmed ID
1688471DOI
10.1126/science.1688471Scopus ID
2-s2.0-0025192609 (requires institutional sign-in at Scopus site) 260 CitationsAbstract
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.
Author List
Tan JC, Nocka K, Ray P, Traktman P, Besmer PMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Base Sequence
Cells, Cultured
DNA
Gene Expression
Homozygote
Liver
Mast Cells
Mice
Molecular Sequence Data
Mutation
Phenotype
Polymerase Chain Reaction
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-kit
RNA
Receptors, Cell Surface
Signal Transduction
