title: The Rho Guanine Nucleotide Exchange Factor DRhoGEF2 Is a Genetic Modifier of the PI3K Pathway in Drosophila.
abstract: 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.
authors.affiliation: Princess Margaret Cancer Center/University Health Network, Toronto, Ontario, Canada.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Princess Margaret Cancer Center/University Health Network, Toronto, Ontario, Canada.
authors.forename: Lily
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Princess Margaret Cancer Center/University Health Network, Toronto, Ontario, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Binari
authors.affiliation: Princess Margaret Cancer Center/University Health Network, Toronto, Ontario, Canada.
authors.forename: Armen
authors.initials: A
authors.lastname: Manoukian
authors.affiliation: Princess Margaret Cancer Center/University Health Network, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Tak
authors.initials: T
authors.lastname: Mak
authors.affiliation: Lunenfeld-Tanenbaum Research Institute/Mount Sinai Hospital, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: McNeill
authors.affiliation: Princess Margaret Cancer Center/University Health Network, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Vuk
authors.initials: V
authors.lastname: Stambolic
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics*; D005123:Eye / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007328:Insulin / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020741:rho GTP-Binding Proteins; C465504:sav protein, Drosophila