Related Experiment Video

Updated: Aug 9, 2026

Heterokaryon Technique for Analysis of Cell Type-specific Localization
09:31

Heterokaryon Technique for Analysis of Cell Type-specific Localization

Published on: March 11, 2011

Nuclear localization and possible functions of receptor tyrosine kinases

Graham Carpenter1

  • 1Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. graham.carpenter@mcmail.vanderbilt.edu

Current Opinion in Cell Biology
|March 22, 2003
PubMed

Insights

Receptor tyrosine kinases, including ErbB-4, are increasingly found in the nucleus. Some evidence suggests these nuclear receptor tyrosine kinases may play a role in gene transcription.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Receptor tyrosine kinases (RTKs) are crucial cell surface receptors.
  • Recent findings suggest RTKs and their ligands may localize to the nucleus.
  • The nuclear functions of RTKs are not fully understood.

Purpose of the Study:

  • To investigate the nuclear localization of receptor tyrosine kinases.
  • To explore the mechanisms of RTK nuclear entry and potential functions.

Main Methods:

  • Analysis of ErbB-4 processing by membrane-localized proteases.
  • Detection of RTKs in the nucleus via biochemical assays.
  • Investigating growth-factor dependency of nuclear localization.

Main Results:

  • The ErbB-4 receptor is proteolytically processed into a soluble cytoplasmic fragment containing the tyrosine kinase domain, which is found in the nucleus.
  • Three other RTKs were detected in the nucleus without proteolytic processing.
  • Nuclear localization of some RTKs is dependent on growth factors.

Conclusions:

  • Receptor tyrosine kinases, including ErbB-4, can translocate to the nucleus.
  • Proteolytic processing is one mechanism for nuclear entry of RTK fragments.
  • Nuclear RTKs may be involved in transcriptional regulation.

More Related Videos

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes09:12

Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes

Published on: December 20, 2019

Related Concept Videos

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...
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
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...
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...
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: