title: Tay bridge is a negative regulator of EGFR signalling and interacts with Erk and Mkp3 in the Drosophila melanogaster wing.
abstract: The regulation of Extracellular regulated kinase (Erk) activity is a key aspect of signalling by pathways activated by extracellular ligands acting through tyrosine kinase transmembrane receptors. In this process, participate proteins with kinase activity that phosphorylate and activate Erk, as well as different phosphatases that inactivate Erk by de-phosphorylation. The state of Erk phosphorylation affects not only its activity, but also its subcellular localization, defining the repertoire of Erk target proteins, and consequently, the cellular response to Erk. In this work, we characterise Tay bridge as a novel component of the EGFR/Erk signalling pathway. Tay bridge is a large nuclear protein with a domain of homology with human AUTS2, and was previously identified due to the neuronal phenotypes displayed by loss-of-function mutations. We show that Tay bridge antagonizes EGFR signalling in the Drosophila melanogaster wing disc and other tissues, and that the protein interacts with both Erk and Mkp3. We suggest that Tay bridge constitutes a novel element involved in the regulation of Erk activity, acting as a nuclear docking for Erk that retains this protein in an inactive form in the nucleus.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa," CSIC and Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Molnar
authors.affiliation: Centro de Biología Molecular "Severo Ochoa," CSIC and Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Jose F
authors.initials: JF
authors.lastname: de Celis
mesh_terms: D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014921:Wings, Animal / Q000378:metabolism
chemical_list: C554283:AUTS2 protein, human; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008024:Ligands; D009687:Nuclear Proteins; D011506:Proteins; D014157:Transcription Factors; C000589448:tay protein, Drosophila; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C086795:rl protein, Drosophila; D054642:Dual Specificity Phosphatase 6; C486844:Mkp3 protein, Drosophila