RRC ID 33093
Author Molnar C, de Celis JF.
Title Tay bridge is a negative regulator of EGFR signalling and interacts with Erk and Mkp3 in the Drosophila melanogaster wing.
Journal PLoS Genet
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.
Volume 9(12)
Pages e1003982
Published 2013-12-12
DOI 10.1371/journal.pgen.1003982
PII PGENETICS-D-13-01385
PMID 24348264
PMC PMC3861119
MeSH Animals Calcium-Calmodulin-Dependent Protein Kinases / genetics* Calcium-Calmodulin-Dependent Protein Kinases / metabolism Cell Nucleus / genetics Cytoskeletal Proteins Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster Dual Specificity Phosphatase 6 / genetics* Dual Specificity Phosphatase 6 / metabolism ErbB Receptors / genetics* ErbB Receptors / metabolism Extracellular Signal-Regulated MAP Kinases / genetics* Extracellular Signal-Regulated MAP Kinases / metabolism Gene Expression Regulation, Developmental Humans Ligands MAP Kinase Signaling System / genetics Nuclear Proteins / genetics* Phosphorylation Proteins / genetics* Proteins / metabolism Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism Transcription Factors Wings, Animal / metabolism
IF 5.175
Times Cited 8
WOS Category GENETICS & HEREDITY
Resource
Drosophila 10079R-2 9375R-1