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) 261 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 PAuthor
Paula Traktman Duncan PhD Emeritus Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH 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
