title: Phosphorylation of Ind by MAP kinase enhances Ind-dependent transcriptional repression.
abstract: The Drosophila neuroectoderm is initially subdivided into three longitudinal domains that give rise to columns of neuroblasts. This subdivision is coordinately accomplished by the action of the signaling pathways, Dorsal and Epidermal Growth Factor Receptor (EGFR), in conjunction with the homeodomain proteins, Ventral nervous system defective, Intermediate neuroblasts defective (Ind) and Muscle Segment Homeobox. We previously demonstrated that Ind expression is activated in response to the EGFR pathway. Here we show that EGF signaling subsequently mediates the direct phosphorylation of Ind by MAP kinase, which enhances the capacity of Ind to repress target genes, such as achaete. Specifically, we show that reduced EGF signaling results in diminished repression of achaete in the intermediate column, despite the presence of high levels of Ind protein. We also demonstrate that ectopic activation of MAP kinase results in the lateral expansion of the Ind expression domain with a corresponding reduction in achaete expression. This regulation is also dependent on the co-repressor, Dichaete. Our data indicate that EGF signaling, acting through MAP kinase, impinges on multiple aspects of Ind regulatory activity. While it has been often demonstrated that MAP kinase phosphorylation of transcriptional repressors attenuates their repressor activity, here we provide an example of phosphorylation enhancing repressor activity.
authors: Kansas State University, College of Veterinary Medicine, Diagnostic Medicine and Pathobiology, Manhattan, KS 66506, USA.
authors: Cade
authors: C
authors: Moses
authors: Aharon
authors: A
authors: Helman
authors: Ze'ev
authors: Z
authors: Paroush
authors: Tonia
authors: T
authors: Von Ohlen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D016297:Mutagenesis, Site-Directed; D055495:Neurogenesis; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055747:SOX Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D055747:SOX Transcription Factors; C103073:D protein, Drosophila; C096010:Dr protein, Drosophila; C116352:IND protein, Drosophila; C089199:ac protein, Drosophila