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Science 290 (5496): 1567-1570

Copyright © 2000 by the American Association for the Advancement of Science

Quantitative Imaging of Lateral ErbB1 Receptor Signal Propagation in the Plasma Membrane

Peter J. Verveer,1* Fred S. Wouters,1* Andrew R. Reynolds,2* Philippe I. H. Bastiaens12dagger

Evidence for a new signaling mechanism consisting of ligand-independent lateral propagation of receptor activation in the plasma membrane is presented. We visualized the phosphorylation of green fluorescent protein (GFP)-tagged ErbB1 (ErbB1-GFP) receptors in cells focally stimulated with epidermal growth factor (EGF) covalently attached to beads. This was achieved by quantitative imaging of protein reaction states in cells by fluorescence resonance energy transfer (FRET) with global analysis of fluorescence lifetime imaging microscopy (FLIM) data. The rapid and extensive propagation of receptor phosphorylation over the entire cell after focal stimulation demonstrates a signaling wave at the plasma membrane resulting in full activation of all receptors.

1 Cell Biology and Cell Biophysics Program, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
2 Cell Biophysics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: philippe.bastiaens{at}embl-heidelberg.de

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