Systems analysis of EGF receptor signaling dynamics with microwestern arrays
Name
nihms-186334.pdf
Description
Accepted version
Size
2.48 MB
Format
Adobe PDF
Checksum (MD5)
a4e479ce0e503a97d83943fdc57904b3
Author(s)
Ciaccio, Mark F
Wagner, Joel P
Chuu, Chih-Pin
Lauffenburger, Douglas A
Jones, Richard B
Date Issued
January 2010
Journal
Nature Methods
Publisher
Springer Science and Business Media LLC
Citation
Ciaccio, Mark F. et al. "Systems analysis of EGF receptor signaling dynamics with microwestern arrays." Nature Methods 7, 2 (January 2010): 148–155 © 2010 Nature America, Inc
Version
Author's final manuscript
Abstract
We describe microwestern arrays, which enable quantitative, sensitive and high-throughput assessment of protein abundance and modifications after electrophoretic separation of microarrayed cell lysates. This method allowed us to measure 91 phosphosites on 67 proteins at six time points after stimulation with five epidermal growth factor (EGF) concentrations in A431 human carcinoma cells. We inferred the connectivities among 15 phosphorylation sites in 10 receptor tyrosine kinases (RTKs) and two sites from Src kinase using Bayesian network modeling and two mutual information-based methods; the three inference methods yielded substantial agreement on the network topology. These results imply multiple distinct RTK coactivation mechanisms and support the notion that small amounts of experimental data collected from phenotypically diverse network states may enable network inference.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Cell Decision Process Center
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nmeth.1418
