The Role of EGF Receptor Ubiquitination in Regulating Its Intracellular Traffic

Traffic. 2012 Feb;13(2):329-37. doi: 10.1111/j.1600-0854.2011.01305.x. Epub 2011 Nov 22.

Abstract

Progression of activated EGF receptor (EGFR) through the endocytic pathway regulates EGFR signaling. Here we show that a non-ubiquitinated EGFR mutant, unable to bind the endosomal-sorting complex required for transport (ESCRT) component, Hrs, is not efficiently targeted onto intraluminal vesicles (ILVs) of multivesicular endosomes/bodies (MVBs). Moreover, ubiquitination and ESCRT engagement of activated EGFR are required for EGF-stimulated ILV formation. Non-ubiquitinated EGFRs enter clathrin-coated tubules emanating from MVBs and show enhanced recycling to the plasma membrane, compared to wild-type EGFR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / cytology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Clathrin / genetics
  • Clathrin / metabolism
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Endosomes / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Epidermal Growth Factor / metabolism
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Multivesicular Bodies / drug effects
  • Multivesicular Bodies / metabolism
  • Multivesicular Bodies / ultrastructure
  • Mutation / physiology
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Protein Subunits / metabolism
  • Protein Transport / drug effects
  • Protein Transport / physiology*
  • Sus scrofa
  • Transfection
  • Transferrin / metabolism
  • Ubiquitination / physiology*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • Clathrin
  • Endosomal Sorting Complexes Required for Transport
  • Protein Subunits
  • Transferrin
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • Epidermal Growth Factor
  • EGFR protein, human
  • ErbB Receptors
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3