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Science 315 (5808): 115-119

Copyright © 2007 by the American Association for the Advancement of Science

Live-Cell Imaging of Enzyme-Substrate Interaction Reveals Spatial Regulation of PTP1B

Ivan A. Yudushkin,1* Andreas Schleifenbaum,1* Ali Kinkhabwala,1* Benjamin G. Neel,2 Carsten Schultz,1 Philippe I. H. Bastiaens1{dagger}

Abstract: Endoplasmic reticulum–localized protein-tyrosine phosphatase PTP1B terminates growth factor signal transduction by dephosphorylation of receptor tyrosine kinases (RTKs). But how PTP1B allows for RTK signaling in the cytoplasm is unclear. In order to test whether PTP1B activity is spatially regulated, we developed a method based on Förster resonant energy transfer for imaging enzyme-substrate (ES) intermediates in live cells. We observed the establishment of a steady-state ES gradient across the cell. This gradient exhibited robustness to cell-to-cell variability, growth factor activation, and RTK localization, which demonstrated spatial regulation of PTP1B activity. Such regulation may be important for generating distinct cellular environments that permit RTK signal transduction and that mediate its eventual termination.

1 European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
2 Cancer Biology Program, Division of Hematology-Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

* These authors contributed equally to this work.

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

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