Related Experiment Video
Updated: Aug 12, 2026
09:16
Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
Published on: September 11, 2015
Mapping a heparin binding site on ErbB-3 epidermal growth factor receptor
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Biochemical and Biophysical Research Communications
|April 27, 2001
Summary
The ErbB-3 receptor specifically binds to heparin, a characteristic not shared by other ErbB family members. This interaction, mediated by a unique amino acid cluster, offers a potential target for therapeutic intervention.
Area of Science:
- Cellular biology
- Molecular biology
- Biochemistry
Background:
- ErbB receptor family signaling is crucial for mammalian development and cancer.
- Heparan sulfate proteoglycans are involved in regulating growth factor signaling.
Purpose of the Study:
- To investigate the interaction between the ErbB-3 receptor and heparin.
- To identify the molecular basis for this interaction and its potential implications.
Main Methods:
- Immobilized heparin binding assays.
- Competition-binding analysis.
- Site-directed mutagenesis.
- Antibody-based detection.
Main Results:
- ErbB-3 receptor uniquely binds to heparin, requiring high ionic strength for dissociation.
- The interaction is specific to highly sulfated heparan sulfate species.
- A basic amino acid cluster (466)KHNRPRR(472) in the ErbB-3 extracellular domain is critical for heparin binding.
- Mutagenesis of this cluster abolishes heparin binding.
- Antibodies against this peptide bind native ErbB-3, indicating its accessibility.
Conclusions:
- ErbB-3 possesses a distinct heparin-binding capability mediated by a specific extracellular motif.
- This interaction represents a novel mechanism for regulating ErbB-3 activity.
- The identified heparin-binding site on ErbB-3 presents a potential therapeutic target for modulating its function.
Related Concept Videos
01:00Enzyme-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...
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...
01:45ER Retrieval Pathway
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
02:38Mitogens 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...
01:26Receptor 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...
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
01:27Transducer 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:
Major types that are helpful drug targets include: