LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans
LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans
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DOI：
10.1111/j.1474-9726.2005.00166.x
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发表时间：
2005-10-01
期刊：
影响因子：
7.8
通讯作者：
Gems, D
中科院分区：
文献类型：
--
作者：
Nanji, M;Hopper, NA;Gems, D
DAF-2胰岛素/胰岛素样生长因子1 （IGF-1）受体通过磷脂酰肌醇3-激酶（PI3K）途径发出信号，控制秀丽隐杆线虫的幼虫形成和成虫寿命。然而上位分析表明信号分叉发生在DAF-2的下游。我们使用上位分析来测试Ras通路（在哺乳动物胰岛素受体的信号传递中起作用）是否在DAF-2的下游起作用。我们发现激活的Ras突变let-60（n1046gf）微弱地抑制daf-2和age-1 （PI3K）突变体的组成性滞育。此外，Ras通路信号的增加部分抑制daf-2突变体的摄食缺陷，而Ras通路信号的减少则增强其摄食缺陷。相反，激活的Ras延长了daf-2突变诱导的寿命，而Ras通路信号的减少部分抑制了daf-2突变。因此，Ras信号通路似乎在幼虫发育过程中与胰岛素/IGF-1信号通路共同作用，但在衰老过程中与之相反。
The DAF-2 insulin/insulin-like growth factor 1 (IGF-1) receptor signals via a phosphatidylinositol 3-kinase (PI3K) pathway to control dauer larva formation and adult longevity in Caenorhabditis elegans. Yet epistasis analysis suggests signal bifurcation downstream of DAF-2. We have used epistasis analysis to test whether the Ras pathway (which plays a role in signaling from mammalian insulin receptors) acts downstream of DAF-2. We find that an activated Ras mutation, let-60(n1046gf), weakly suppresses constitutive dauer diapause in daf-2 and age-1 (PI3K) mutants. Moreover, increased Ras pathway signaling partially suppresses the daf-2 mutant feeding defect, while reduced Ras pathway signaling enhances it. By contrast, activated Ras extends the longevity induced by mutation of daf-2, while reduced Ras pathway signaling partially suppresses it. Thus, Ras pathway signaling appears to act with insulin/IGF-1 signaling during larval development, but against it during aging.