Open AccessLET‐60 RAS modulates effects of insulin/IGF‐1 signaling on development and aging in Caenorhabditis elegans
Author(s) -
Nanji Manoj,
Hopper Neil A.,
Gems David
Publication year - 2005
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2005.00166.x
Subject(s) - biology , caenorhabditis elegans , signal transduction , insulin receptor , microbiology and biotechnology , proto oncogene proteins c akt , mutant , pi3k/akt/mtor pathway , tor signaling , insulin like growth factor , mutation , phosphatidylinositol , insulin , receptor , genetics , growth factor , endocrinology , gene , insulin resistance
Summary 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.