Related Experiment Video

Updated: May 4, 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

9.7K

erbB3 is an active tyrosine kinase capable of homo- and heterointeractions

Mara P Steinkamp1, Shalini T Low-Nam, Shujie Yang

  • 1Department of Pathology, University of New Mexico, Albuquerque, New Mexico, USA.

Molecular and Cellular Biology
|January 1, 2014
PubMed

Insights

The study reveals that erbB3, previously thought inactive, gains kinase activity upon heregulin stimulation. This activation is dependent on interactions with erbB2, offering new insights into targeted cancer therapies.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • The erbB3 receptor is often considered a "dead" kinase.
  • It plays a role in resistance to erbB-targeted cancer therapies.

Purpose of the Study:

  • To investigate the mechanisms of erbB3 activation.
  • To explore the role of erbB2 in erbB3 kinase activity.
  • To understand erbB3 dimerization in live cells.

Main Methods:

  • Heregulin stimulation to induce erbB3 activity.
  • Site-directed mutagenesis of lysine 723 in erbB3.
  • Treatment with lapatinib and pertuzumab to block erbB2.
  • Single-particle tracking of quantum dot-labeled receptors on live cells.

Main Results:

  • Heregulin stimulation markedly upregulates erbB3 kinase activity.
  • Activated erbB3 phosphorylates exogenous substrates, dependent on lysine 723.
  • erbB2 activation of erbB3 is crucial and can occur even with disproportionate receptor levels.
  • Transient erbB3/erbB2 heterointeractions precede erbB3 homodimer signaling competence.

Conclusions:

  • erbB3 possesses latent kinase activity that can be triggered by heregulin.
  • erbB2 acts as a crucial activator of erbB3 kinase function.
  • Understanding these interactions is key for developing strategies against therapeutic resistance in erbB-family driven cancers.

More Related Videos

Dissecting Multi-protein Signaling Complexes by Bimolecular Complementation Affinity Purification BiCAP06:45

Dissecting Multi-protein Signaling Complexes by Bimolecular Complementation Affinity Purification BiCAP

Published on: June 15, 2018

6.6K
Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

5.7K

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...
15.5K
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...
64.6K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

5.1K
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:
4.4K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.3K
Epistasis01:39

Epistasis

In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
37.3K