Tay bridge is a negative regulator of EGFR signalling and interacts with Erk and Mkp3 in the Drosophila melanogaster wing

PLoS Genetics
Cristina Molnar, Jose F de Celis

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.

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Citations

Jan 9, 2020·Molecular Biology of the Cell·Sayantanee PaulAlexey Veraksa
Sep 17, 2020·International Journal of Molecular Sciences·Daniel R LathenAdrian Rothenfluh
Oct 3, 2021·G3 : Genes - Genomes - Genetics·Ana López-VareaJose F de Celis

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Datasets Mentioned

BETA
SD06439

Methods Mentioned

BETA
co-immunoprecipitation
pull-down
Co-IPs
Pull down
pulldowns
immunoprecipitation
PCR
pulldown

Software Mentioned

ImageJ
Jalview

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