Sternberg P W, Golden A, Han M
Division of Biology, California Institute of Technology, Pasadena 91125.
Philos Trans R Soc Lond B Biol Sci. 1993 Jun 29;340(1293):259-65. doi: 10.1098/rstb.1993.0066.
During Caenorhabditis elegans vulval induction, multipotent precursors respond to an inductive signal by generating vulval cells as opposed to non-specialized epidermal cells. Both classical and 'reverse' genetic approaches have revealed that a cascade of nematode homologues of mammalian proto-oncogenes is necessary for induction of the vulva. The inductive signal is a growth factor encoded by the lin-3 gene and its candidate receptor is a tyrosine kinase encoded by the let-23 gene. let-23 acts via a Ras protein encoded by the let-60 gene. A nematode homologue of mammalian raf family protein serine/threonine kinases has been cloned and found to be encoded by the lin-45 gene. Dominant negative lin-45 raf mutants prevent vulval induction. A recessive lin-45 raf mutation prevents the excessive vulval differentiation caused by activated ras, indicating that raf might act downstream of ras during vulval induction.
在秀丽隐杆线虫的外阴诱导过程中,多能前体细胞通过生成外阴细胞而非非特化的表皮细胞来响应诱导信号。经典遗传学方法和“反向”遗传学方法均已表明,一系列哺乳动物原癌基因的线虫同源物对于外阴诱导是必需的。诱导信号是由lin-3基因编码的一种生长因子,其候选受体是由let-23基因编码的一种酪氨酸激酶。let-23通过由let-60基因编码的Ras蛋白发挥作用。已克隆出一种哺乳动物raf家族蛋白丝氨酸/苏氨酸激酶的线虫同源物,发现它由lin-45基因编码。显性负性lin-45 raf突变体可阻止外阴诱导。隐性lin-45 raf突变可阻止由激活的ras引起的过度外阴分化,这表明raf可能在外阴诱导过程中作用于ras的下游。