Related Experiment Video

Updated: Jun 15, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Characterization of a domain that transiently converts class 2 DYRKs into intramolecular tyrosine kinases

Ross Kinstrie1, Nathan Luebbering, Diego Miranda-Saavedra

  • 11Department of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.

Science Signaling
|March 4, 2010
PubMed

Insights

Researchers discovered a new domain, the NAPA domain, in dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs). This domain acts like a chaperone, enabling DYRKs to autophosphorylate and activate themselves, a process conserved across species.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Enzymology

Background:

  • Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) are crucial enzymes that regulate cellular processes through phosphorylation.
  • DYRKs require autophosphorylation of an activation loop tyrosine residue for their serine-threonine kinase activity.
  • This autophosphorylation is an intramolecular event occurring during a transient protein maturation stage.

Purpose of the Study:

  • To investigate the mechanism of activation loop tyrosine autophosphorylation in DYRKs.
  • To identify novel domains involved in the regulation of DYRK kinase activity.
  • To understand the evolutionary conservation of DYRK activation mechanisms.

Main Methods:

  • Bioinformatics analysis to identify conserved domains.
  • Site-directed mutagenesis to probe domain function.
  • Biochemical assays to assess kinase activity and autophosphorylation.

Main Results:

  • A conserved N-terminal domain, termed the NAPA domain, was identified in class 2 DYRKs.
  • The NAPA domain is essential for the autophosphorylation of the activation loop tyrosine.
  • The NAPA domain is not required for the subsequent phosphorylation of substrates on serine and threonine residues.
  • The NAPA domain appears to facilitate an intramolecular kinase function for autophosphorylation.

Conclusions:

  • The NAPA domain acts as a molecular chaperone, promoting the intramolecular autophosphorylation of the DYRK activation loop tyrosine.
  • This mechanism is critical for the functional activation of DYRK kinases.
  • The ancient conservation of the NAPA domain suggests a primordial role in protein kinase activation.

More Related Videos

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein11:23

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Related Concept Videos

Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...