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The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila.

PLoS One. 2016 Mar 25;11(3):e0152259. eCollection 2016
Ying-Ju Chang 1 , Lily Zhou 1 , Richard Binari 1 , Armen Manoukian 1 , Tak Mak 2 , Helen McNeill 3 , Vuk Stambolic 2
Ying-Ju Chang 1 , Lily Zhou 1 , Richard Binari 1 , Armen Manoukian 1 , Tak Mak 2 , Helen McNeill 3 , Vuk Stambolic 2
+ et al

[No authors listed]

Author information
  • 1 Princess Margaret Cancer Center/University Health Network, Toronto, Ontario, Canada.
  • 2 Department of Medical Biophysics, University of Toronto, Toronto, Canada.
  • 3 Department of Molecular Genetics, University of Toronto, Toronto, Canada.
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摘要


The insulin/IGF-1 signaling pathway mediates various physiological processes associated with human health. Components of this pathway are highly conserved throughout eukaryotic evolution. In Drosophila, the PTEN ortholog and its mammalian counterpart downregulate insulin/IGF signaling by antagonizing the PI3-kinase function. From a dominant loss-of-function genetic screen, we discovered that mutations of a Dbl-family member, the guanine nucleotide exchange factor DRhoGEF2 (DRhoGEF22(l)04291), suppressed the PTEN-overexpression eye phenotype. dAkt/dPKB phosphorylation, a measure of PI3K signaling pathway activation, increased in the eye discs from the heterozygous DRhoGEF2 wandering third instar larvae. Overexpression of DRhoGEF2, and it's functional mammalian ortholog PDZ-RhoGEF (ArhGEF11), at various stages of eye development, resulted in both dPKB/Akt-dependent and -independent phenotypes, reflecting the complexity in the crosstalk between PI3K and Rho signaling in Drosophila.

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