Nocka K, Majumder S, Chabot B, Ray P, Cervone M, Bernstein A, Besmer P
Molecular Biology Program, Sloan Kettering Institute, New York, New York.
Genes Dev. 1989 Jun;3(6):816-26. doi: 10.1101/gad.3.6.816.
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.
原癌基因c-kit是一种针对未知配体的跨膜酪氨酸蛋白激酶受体,最近被证明定位于小鼠的显性白斑位点(W)。W位点的突变会影响造血的各个方面,以及发育过程中原始生殖细胞和成黑素细胞的增殖和/或迁移。在这里,我们表明c-kit在已知受胎儿和成人红细胞生成组织、肥大细胞以及神经嵴衍生的黑素细胞中W突变影响的组织中表达。我们证明,c-kit相关的酪氨酸特异性蛋白激酶在W/WV肥大细胞中功能受损,从而为理解这些突变导致的发育缺陷提供了分子基础。