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Related Concept Videos

Receptor Downregulation in MVBs01:15

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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.
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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...
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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...
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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.
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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Updated: Jul 15, 2025

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EGFR trafficking: effect of dimerization, dynamics, and mutation.

Destiny F Schultz1, Daniel D Billadeau1,2, Seetharama D Jois3

  • 1Department of Immunology, Mayo Clinic, Rochester, MN, United States.

Frontiers in Oncology
|September 27, 2023
PubMed
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Dysregulated epidermal growth factor receptor (EGFR) signaling drives cancer. Targeting EGFR trafficking, alongside tyrosine kinase inhibitors, may overcome treatment resistance by controlling receptor down-regulation.

Keywords:
EGFR traffickingcancerclathrin-mediated endocytosisdimerizationlysosome

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Aberrant epidermal growth factor receptor (EGFR) signaling, including spontaneous dimerization, is implicated in various cancers.
  • Normal EGFR signaling requires attenuation through internalization, endosomal sorting, and lysosomal degradation (receptor down-regulation).

Purpose of the Study:

  • To review EGFR structure, trafficking pathways, and altered surface expression in cancer.
  • To explore the therapeutic potential of targeting EGFR trafficking in combination with existing cancer treatments.

Main Methods:

  • Literature review focusing on EGFR biology and cancer.
  • Analysis of mechanisms underlying EGFR trafficking and its role in treatment resistance.

Main Results:

  • Altered EGFR trafficking contributes to tumor resistance to current therapies.
  • Targeting EGFR trafficking presents a promising strategy for enhancing cancer treatment efficacy.

Conclusions:

  • Understanding EGFR trafficking is crucial for developing effective cancer therapies.
  • Combination strategies involving EGFR trafficking inhibitors and tyrosine kinase inhibitors warrant further investigation.