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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...
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:
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...

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Updated: Jun 27, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Ligand-induced ErbB receptor dimerization.

Mark A Lemmon1

  • 1Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104-6059, USA. mlemmon@mail.med.upenn.edu

Experimental Cell Research
|November 29, 2008
PubMed
Summary
This summary is machine-generated.

Structural studies reveal how EGF receptor activation occurs, but cell-surface studies suggest different mechanisms. Reconciling these findings is key to understanding ErbB receptor function and allosteric regulation.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Structural Biology

Background:

  • Epidermal Growth Factor (EGF) receptor and ErbB family members are crucial receptor tyrosine kinases.
  • Structural studies offer insights into ligand-induced homodimerization and activation.
  • ErbB2 exhibits unique properties, including oncogenic potential via overexpression without a known ligand.

Purpose of the Study:

  • To reconcile discrepancies between structural studies and cell-surface binding data for EGF receptor activation.
  • To integrate findings from studies of isolated ErbB receptor regions and intact cell-surface receptors.
  • To propose a unified model for ErbB receptor function as allosterically regulated enzymes.

Main Methods:

  • Review of structural studies on ErbB receptor extracellular regions in solution.
  • Analysis of cell-surface binding studies of intact EGF receptors.
  • Comparative analysis of structural predictions and experimental observations.

Main Results:

  • Structural studies suggest positive cooperativity in EGF binding and receptor dimerization.
  • Cell-surface studies indicate negative cooperativity in EGF binding.
  • Discrepancies highlight missing mechanistic components in current structural models.

Conclusions:

  • Reconciling solution and cell-surface data is essential for a complete understanding of ErbB receptor mechanisms.
  • Considering intact ErbB receptors as allosterically regulated enzymes is crucial.
  • Integrating structural and cellular studies provides a comprehensive picture of receptor function.