Katz W S, Lesa G M, Yannoukakos D, Clandinin T R, Schlessinger J, Sternberg P W
Howard Hughes Medical Institute, California Institute of Technology, Pasadena, 91125, USA.
Mol Cell Biol. 1996 Feb;16(2):529-37. doi: 10.1128/MCB.16.2.529.
The let-23 gene encodes a Caenorhabditis elegans homolog of the epidermal growth factor receptor (EGFR) necessary for vulval development. We have characterized a mutation of let-23 that activates the receptor and downstream signal transduction, leading to excess vulval differentiation. This mutation alters a conserved cysteine residue in the extracellular domain and is the first such point mutation in the EGFR subfamily of tyrosine kinases. Mutation of a different cysteine in the same subdomain causes a strong loss-of-function phenotype, suggesting that cysteines in this region are important for function and nonequivalent. Vulval precursor cells can generate either of two subsets of vulval cells (distinct fates) in response to sa62 activity. The fates produced depended on the copy number of the mutation, suggesting that quantitative differences in receptor activity influence the decision between these two fates.
let-23基因编码一种秀丽隐杆线虫表皮生长因子受体（EGFR）的同源物，该同源物是外阴发育所必需的。我们已经鉴定出let-23的一种突变，该突变激活了受体和下游信号转导，导致外阴过度分化。这种突变改变了细胞外结构域中一个保守的半胱氨酸残基，并且是酪氨酸激酶EGFR亚家族中的首个此类点突变。同一亚结构域中另一个半胱氨酸的突变会导致强烈的功能丧失表型，这表明该区域中的半胱氨酸对功能很重要且不等同。外阴前体细胞可以响应sa62活性而产生两种外阴细胞亚群（不同的命运）中的任何一种。所产生的命运取决于突变的拷贝数，这表明受体活性的定量差异会影响这两种命运之间的抉择。
