Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction

Nat Biotechnol. 2004 Feb;22(2):198-203. doi: 10.1038/nbt929. Epub 2004 Jan 4.


The erbB/HER family of transmembrane receptor tyrosine kinases (RTKs) mediate cellular responses to epidermal growth factor (EGF) and related ligands. We have imaged the early stages of RTK-dependent signaling in living cells using: (i) stable expression of erbB1/2/3 fused with visible fluorescent proteins (VFPs), (ii) fluorescent quantum dots (QDs) bearing epidermal growth factor (EGF-QD) and (iii) continuous confocal laser scanning microscopy and flow cytometry. Here we demonstrate that EGF-QDs are highly specific and potent in the binding and activation of the EGF receptor (erbB1), being rapidly internalized into endosomes that exhibit active trafficking and extensive fusion. EGF-QDs bound to erbB1 expressed on filopodia revealed a previously unreported mechanism of retrograde transport to the cell body. When erbB2-monomeric yellow fluorescent protein (mYFP) or erbB3-monomeric Citrine (mCitrine) were coexpressed with erbB1, the rates and extent of endocytosis of EGF-QD and the RTK-VFP demonstrated that erbB2 but not erbB3 heterodimerizes with erbB1 after EGF stimulation, thereby modulating EGF-induced signaling. QD-ligands will find widespread use in basic research and biotechnological developments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism*
  • Cricetinae
  • Endosomes / metabolism
  • Endosomes / ultrastructure
  • Epidermal Growth Factor / metabolism
  • Humans
  • Motion
  • Oncogene Proteins v-erbB / metabolism
  • Protein Binding
  • Protein Interaction Mapping / methods*
  • Protein Transport / physiology*
  • Quantum Dots*
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction / physiology*
  • Spectrometry, Fluorescence / methods*


  • Oncogene Proteins v-erbB
  • Receptors, Cell Surface
  • Epidermal Growth Factor