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

Diane S. Lidke, Peter Nagy, Rainer Heintzmann, Donna J. Arndt-Jovin, Janine Nicole Post, Hernan E. Grecco, Elizabeth A. Jares-Erijman, Thomas M. Jovin

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717 Citations (Scopus)

Abstract

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
Original languageUndefined
Pages (from-to)198-203
JournalNature biotechnology
Volume22
DOIs
Publication statusPublished - 2004

Keywords

  • IR-77328

Cite this

Lidke, D. S., Nagy, P., Heintzmann, R., Arndt-Jovin, D. J., Post, J. N., Grecco, H. E., ... Jovin, T. M. (2004). Quantum dot ligands provide new insights into erbB/HER receptor–mediated signal transduction. Nature biotechnology, 22, 198-203. https://doi.org/10.1038/nbt929