Pilgrim D, McGregor A, Jäckle P, Johnson T, Hansen D
Department of Biological Sciences, University of Alberta, Edmonton, Canada.
Mol Biol Cell. 1995 Sep;6(9):1159-71. doi: 10.1091/mbc.6.9.1159.
The genetic and molecular analysis of genes involved in the regulation of sex determination in Caenorhabditis elegans suggests that the gene fem-2 plays an important role in regulating a pathway transducing a non-cell-autonomous signal to a nuclear transcription factor. The wild-type fem-2 gene was cloned by identifying sequences from the C. elegans physical map that could restore normal Fem-2 function to homozygous mutant fem-2 transgenic animals. cDNA sequences mapping to the minimal rescuing region correspond to an open reading frame with a sequence similar to protein phosphatase 2C enzymes from systems as diverse as yeast, humans, and plants, but the alignments suggest that FEM-2 falls into a separate class of proteins than the canonical homologues. Several fem-2 mutant alleles were sequenced, and the mutations are predicted to cause protein changes consistent with their observed phenotypes, such as missense mutations in conditional alleles, and a nonsense mutation in a predicted null allele. This is the first evidence implicating phosphorylation and/or dephosphorylation as a control mechanism in C. elegans sex determination.
对秀丽隐杆线虫性别决定调控相关基因的遗传和分子分析表明,fem-2基因在调控一条将非细胞自主性信号转导至核转录因子的信号通路中发挥重要作用。野生型fem-2基因是通过从秀丽隐杆线虫物理图谱中鉴定出能够将正常Fem-2功能恢复至纯合突变型fem-2转基因动物的序列而克隆得到的。定位于最小拯救区域的cDNA序列对应于一个开放阅读框,其序列与来自酵母、人类和植物等多种系统的蛋白磷酸酶2C酶相似,但比对结果表明FEM-2属于与典型同源物不同的一类蛋白质。对多个fem-2突变等位基因进行了测序,预测这些突变会导致与其观察到的表型一致的蛋白质变化,如条件等位基因中的错义突变以及预测的无效等位基因中的无义突变。这是首个表明磷酸化和/或去磷酸化作为秀丽隐杆线虫性别决定控制机制的证据。