PMID- 14704683 OWN - NLM STAT- MEDLINE DCOM- 20040907 LR - 20220309 IS - 1087-0156 (Print) IS - 1087-0156 (Linking) VI - 22 IP - 2 DP - 2004 Feb TI - Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. PG - 198-203 AB - 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. FAU - Lidke, Diane S AU - Lidke DS AD - Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Gottingen, Germany. dlidke@gwdg.de FAU - Nagy, Peter AU - Nagy P FAU - Heintzmann, Rainer AU - Heintzmann R FAU - Arndt-Jovin, Donna J AU - Arndt-Jovin DJ FAU - Post, Janine N AU - Post JN FAU - Grecco, Hernan E AU - Grecco HE FAU - Jares-Erijman, Elizabeth A AU - Jares-Erijman EA FAU - Jovin, Thomas M AU - Jovin TM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040104 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 RN - 0 (Oncogene Proteins v-erbB) RN - 0 (Receptors, Cell Surface) RN - 62229-50-9 (Epidermal Growth Factor) SB - IM CIN - Nat Biotechnol. 2004 Feb;22(2):169-70. PMID: 14755288 MH - Animals MH - Cell Membrane/*metabolism MH - Cricetinae MH - Endosomes/metabolism/ultrastructure MH - Epidermal Growth Factor/metabolism MH - Humans MH - Motion MH - Oncogene Proteins v-erbB/metabolism MH - Protein Binding MH - Protein Interaction Mapping/*methods MH - Protein Transport/*physiology MH - *Quantum Dots MH - Receptors, Cell Surface/*metabolism MH - Signal Transduction/*physiology MH - Spectrometry, Fluorescence/*methods EDAT- 2004/01/06 05:00 MHDA- 2004/09/08 05:00 CRDT- 2004/01/06 05:00 PHST- 2003/10/24 00:00 [received] PHST- 2003/11/24 00:00 [accepted] PHST- 2004/01/06 05:00 [pubmed] PHST- 2004/09/08 05:00 [medline] PHST- 2004/01/06 05:00 [entrez] AID - nbt929 [pii] AID - 10.1038/nbt929 [doi] PST - ppublish SO - Nat Biotechnol. 2004 Feb;22(2):198-203. doi: 10.1038/nbt929. Epub 2004 Jan 4.