Live-Cell Imaging of Enzyme-Substrate Interaction Reveals Spatial Regulation of PTP1B
SciencePublished 5 January 2007
Ivan Yudushkin, Andreas Schleifenbaum, Ali Kinkhabwala, Benjamin G. Neel, Carsten Schultz, Philippe I. H. Bastiaens
Citations146
SJR quartileQ1
SJR score10.42
SNIP6.62
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TL;DR
A method based on Förster resonant energy transfer for imaging enzyme-substrate (ES) intermediates in live cells demonstrated spatial regulation of PTP1B activity, which may be important for generating distinct cellular environments that permit RTK signal transduction and that mediate its eventual termination.
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.
Keywords
Immunology and MicrobiologyBiochemistry, Genetics and Molecular Biology
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