Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice--evidence for an impaired c-kit kinase in mutant mice.
The proto-oncogene c-kit, a transmembrane tyrosine protein kinase receptor for an unknown ligand, was shown recently to map to the dominant white spotting locus (W) of the mouse. Mutations at the W locus affect various aspects of hematopoiesis, as well as the proliferation and/or migration of primordial germ cells and melanoblasts during development. Here, we show that c-kit is expressed in tissues known to be affected by W mutations in fetal and adult erythropoietic tissues, mast cells, and neural-crest-derived melanocytes. We demonstrate that the c-kit associated tyrosine-specific protein kinase is functionally impaired in W/WV mast cells, thus providing a molecular basis for understanding the developmental defects that result from these mutations.
Nocka
K
K
Molecular Biology Program, Sloan Kettering Institute, New York, New York.
Majumder
S
S
Chabot
B
B
Ray
P
P
Cervone
M
M
Bernstein
A
A
Besmer
P
P
D000483:Alleles; D000748:Anemia, Macrocytic / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D002465:Cell Movement; D005314:Embryonic and Fetal Development; D005804:Genes, Lethal; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000201:enzymology; D006579:Heterozygote; D008099:Liver / Q000196:embryology / Q000201:enzymology; D008407:Mast Cells / Q000201:enzymology; D008544:Melanocytes / Q000201:enzymology; D008546:Melanoma, Experimental; D051379:Mice; D008817:Mice, Mutant Strains / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D009432:Neural Crest / Q000473:pathology; D009928:Organ Specificity; D010859:Pigmentation Disorders / Q000196:embryology / Q000201:enzymology / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000201:enzymology
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit