Defining novel targets and functions of the protein kinase DYRK2
type: CreativeWork
description: Protein post-translational modifications (PTMs) are an essential and conserved mechanism that allows eukaryotic cells to coordinate rapid responses to changing environmental conditions. Protein kinases, comprising a large eukaryotic superfamily of ~518 proteins, catalyse protein phosphorylation. Dual-specificity tyrosine-phosphorylation regulated kinases (DYRKs) are a family of protein kinases that are distantly related to the mitogen-activated protein kinases (MAPKs) and cyclin-dependent protein kinases (CDKs). Hundreds of substrates and interacting partner proteins have been identified for MAPKs and CDKs, whereas relatively little is known about the substrates and functions of DYRKs. DYRKs are evolutionarily conserved in protists, plants, fungi and animals; they widely function in cell cycle regulation, cytokinesis and cell differentiation, but they also orchestrate signalling responses to nitrosative, oxidative, nutritional, heat and osmotic stress. The five mammalian DYRKs can be divided into two subgroups based on their sequence homology: class I (DYRK1A, DYRK1B) and class II (DYRK2, DYRK3, DYRK4). Remarkable effort has been spent on identifying the roles of human DYRK1A, a Down syndrome candidate gene that is strongly implicated in neurogenesis, yet the physiological functions and substrates of the remaining human DYRK kinases are poorly characterised. This project employed a top-down experimental design with three main objectives: 1) assessing global cellular functions of DYRK2 using proteomic and transcriptomic analyses to identify protein and gene targets that are downstream of DYRK2; 2) validating novel DYRK2 substrates and localising the phospho-acceptor site(s) on target proteins using molecular biology and biochemical assays and 3) elucidating the biochemical purpose of DYRK2-substrate interactions identified in earlier experiments using DYRK2 knockout cells generated by CRISPR-Cas9 technology. Since DYRKs undergo cis-autoactivation during translation, …
abstract: Protein post-translational modifications (PTMs) are an essential and conserved mechanism that allows eukaryotic cells to coordinate rapid responses to changing environmental conditions. Protein kinases, comprising a large eukaryotic superfamily of ~518 proteins, catalyse protein phosphorylation. Dual-specificity tyrosine-phosphorylation regulated kinases (DYRKs) are a family of protein kinases that are distantly related to the mitogen-activated protein kinases (MAPKs) and cyclin-dependent protein kinases (CDKs). Hundreds of substrates and interacting partner proteins have been identified for MAPKs and CDKs, whereas relatively little is known about the substrates and functions of DYRKs. DYRKs are evolutionarily conserved in protists, plants, fungi and animals; they widely function in cell cycle regulation, cytokinesis and cell differentiation, but they also orchestrate signalling responses to nitrosative, oxidative, nutritional, heat and osmotic stress. The five mammalian DYRKs can be divided into two subgroups based on their sequence homology: class I (DYRK1A, DYRK1B) and class II (DYRK2, DYRK3, DYRK4). Remarkable effort has been spent on identifying the roles of human DYRK1A, a Down syndrome candidate gene that is strongly implicated in neurogenesis, yet the physiological functions and substrates of the remaining human DYRK kinases are poorly characterised. This project employed a top-down experimental design with three main objectives: 1) assessing global cellular functions of DYRK2 using proteomic and transcriptomic analyses to identify protein and gene targets that are downstream of DYRK2; 2) validating novel DYRK2 substrates and localising the phospho-acceptor site(s) on target proteins using molecular biology and biochemical assays and 3) elucidating the biochemical purpose of DYRK2-substrate interactions identified in earlier experiments using DYRK2 knockout cells generated by CRISPR-Cas9 technology. Since DYRKs undergo cis-autoactivation during translation, …
author: Huntly, Rachael Louise
language: en
keywords: DYRK, DYRKs, DYRK2, Hippo signalling, Hippo, YAP, p62, SQSTM1, phosphorylation, substrates, RNA processing, CRISPR, Mass spectrometry, protein kinase, kinase, DYRK1B, DYRK1A, DYRK3, DYRK4, SILAC, Mitosis, DNA damage, Screening
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/4bbb59a7-890d-43cd-9c4b-118999d0d59d/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2020-07-17
date modified: 2026-07-22T22:24:00Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.51870