title: Nemo phosphorylates Eyes absent and enhances output from the Eya-Sine oculis transcriptional complex during Drosophila retinal determination.
abstract: The retinal determination gene network comprises a collection of transcription factors that respond to multiple signaling inputs to direct Drosophila eye development. Previous genetic studies have shown that nemo (nmo), a gene encoding a proline-directed serine/threonine kinase, can promote retinal specification through interactions with the retinal determination gene network, although the molecular point of cross-talk was not defined. Here, we report that the Nemo kinase positively and directly regulates Eyes absent (Eya). Genetic assays show that Nmo catalytic activity enhances Eya-mediated ectopic eye formation and potentiates induction of the Eya-Sine oculis (So) transcriptional targets dachshund and lozenge. Biochemical analyses demonstrate that Nmo forms a complex with and phosphorylates Eya at two consensus mitogen-activated protein kinase (MAPK) phosphorylation sites. These same sites appear crucial for Nmo-mediated activation of Eya function in vivo. Thus, we propose that Nmo phosphorylation of Eya potentiates its transactivation function to enhance transcription of Eya-So target genes during eye specification and development.
authors.affiliation: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Santiago A
authors.initials: SA
authors.lastname: Morillo
authors.forename: Lorena R
authors.initials: LR
authors.lastname: Braid
authors.forename: Esther M
authors.initials: EM
authors.lastname: Verheyen
authors.forename: Ilaria
authors.initials: I
authors.lastname: Rebay
mesh_terms: D000818:Animals; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000502:physiology*; D005123:Eye / Q000196:embryology*; D005136:Eye Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D038081:Organogenesis; D010766:Phosphorylation; D012160:Retina / Q000196:embryology / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; C087345:So protein, Drosophila; C092694:eya protein, Drosophila; D020928:Mitogen-Activated Protein Kinases; C110707:nmo protein, Drosophila