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

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 antagonizin...

Full description

Bibliographic Details
Main Authors: Ying-Ju Chang, Lily Zhou, Richard Binari, Armen Manoukian, Tak Mak, Helen McNeill, Vuk Stambolic
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4807833?pdf=render
_version_ 1819102434220310528
author Ying-Ju Chang
Lily Zhou
Richard Binari
Armen Manoukian
Tak Mak
Helen McNeill
Vuk Stambolic
author_facet Ying-Ju Chang
Lily Zhou
Richard Binari
Armen Manoukian
Tak Mak
Helen McNeill
Vuk Stambolic
author_sort Ying-Ju Chang
collection DOAJ
description 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.
first_indexed 2024-12-22T01:34:30Z
format Article
id doaj.art-e92396b3a24f482aa660954c8987946b
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-22T01:34:30Z
publishDate 2016-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-e92396b3a24f482aa660954c8987946b2022-12-21T18:43:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015225910.1371/journal.pone.0152259The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila.Ying-Ju ChangLily ZhouRichard BinariArmen ManoukianTak MakHelen McNeillVuk StambolicThe 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.http://europepmc.org/articles/PMC4807833?pdf=render
spellingShingle Ying-Ju Chang
Lily Zhou
Richard Binari
Armen Manoukian
Tak Mak
Helen McNeill
Vuk Stambolic
The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila.
PLoS ONE
title The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila.
title_full The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila.
title_fullStr The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila.
title_full_unstemmed The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila.
title_short The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila.
title_sort rho guanine nucleotide exchange factor drhogef2 is a genetic modifier of the pi3k pathway in drosophila
url http://europepmc.org/articles/PMC4807833?pdf=render
work_keys_str_mv AT yingjuchang therhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT lilyzhou therhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT richardbinari therhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT armenmanoukian therhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT takmak therhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT helenmcneill therhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT vukstambolic therhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT yingjuchang rhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT lilyzhou rhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT richardbinari rhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT armenmanoukian rhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT takmak rhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT helenmcneill rhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila
AT vukstambolic rhoguaninenucleotideexchangefactordrhogef2isageneticmodifierofthepi3kpathwayindrosophila