Chang C, Hopper N A, Sternberg P W
HHMI and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
EMBO J. 2000 Jul 3;19(13):3283-94. doi: 10.1093/emboj/19.13.3283.
Vulval induction in Caenorhabditis elegans has helped define an evolutionarily conserved signal transduction pathway from receptor tyrosine kinases (RTKs) through the adaptor protein SEM-5 to RAS. One component present in other organisms, a guanine nucleotide exchange factor for Ras, has been missing in C.ELEGANS: To understand the regulation of this pathway it is crucial to have all positive-acting components in hand. Here we describe the identification, cloning and genetic characterization of C.ELEGANS: SOS-1, a putative guanine nucleotide exchanger for LET-60 RAS. RNA interference experiments suggest that SOS-1 participates in RAS-dependent signaling events downstream of LET-23 EGFR, EGL-15 FGFR and an unknown RTK. We demonstrate that the previously identified let-341 gene encodes SOS-1. Analyzing vulval development in a let-341 null mutant, we find an SOS-1-independent pathway involved in the activation of RAS signaling. This SOS-1-independent signaling is not inhibited by SLI-1/Cbl and is not mediated by PTP-2/SHP, raising the possibility that there could be another RasGEF.
秀丽隐杆线虫中的外阴诱导有助于确定一条从受体酪氨酸激酶（RTK）通过衔接蛋白SEM-5到RAS的进化保守信号转导途径。在其他生物中存在的一个成分，即Ras的鸟嘌呤核苷酸交换因子，在秀丽隐杆线虫中一直缺失：为了理解这条途径的调控，掌握所有起积极作用的成分至关重要。在这里，我们描述了秀丽隐杆线虫SOS-1的鉴定、克隆和遗传特征，SOS-1是一种假定的LET-60 RAS鸟嘌呤核苷酸交换因子。RNA干扰实验表明，SOS-1参与LET-23表皮生长因子受体、EGL-15成纤维细胞生长因子受体和一种未知RTK下游的RAS依赖性信号事件。我们证明，先前鉴定的let-341基因编码SOS-1。通过分析let-341基因敲除突变体中的外阴发育，我们发现了一条不依赖SOS-1的途径参与RAS信号的激活。这种不依赖SOS-1的信号传导不受SLI-1/Cbl抑制，也不由PTP-2/SHP介导，这增加了可能存在另一种RasGEF的可能性。
