| Title |
A Comprehensive, Multi-Scale Dynamical Model of ErbB Receptor Signal Transduction in Human Mammary Epithelial Cells
|
|---|---|
| Published in |
PLOS ONE, April 2013
|
| DOI | 10.1371/journal.pone.0061757 |
| Pubmed ID | |
| Authors |
Tomáš Helikar, Naomi Kochi, Bryan Kowal, Manjari Dimri, Mayumi Naramura, Srikumar M. Raja, Vimla Band, Hamid Band, Jim A. Rogers |
| Abstract |
The non-receptor tyrosine kinase Src and receptor tyrosine kinase epidermal growth factor receptor (EGFR/ErbB1) have been established as collaborators in cellular signaling and their combined dysregulation plays key roles in human cancers, including breast cancer. In part due to the complexity of the biochemical network associated with the regulation of these proteins as well as their cellular functions, the role of Src in EGFR regulation remains unclear. Herein we present a new comprehensive, multi-scale dynamical model of ErbB receptor signal transduction in human mammary epithelial cells. This model, constructed manually from published biochemical literature, consists of 245 nodes representing proteins and their post-translational modifications sites, and over 1,000 biochemical interactions. Using computer simulations of the model, we find it is able to reproduce a number of cellular phenomena. Furthermore, the model predicts that overexpression of Src results in increased endocytosis of EGFR in the absence/low amount of the epidermal growth factor (EGF). Our subsequent laboratory experiments also suggest increased internalization of EGFR upon Src overexpression under EGF-deprived conditions, further supporting this model-generated hypothesis. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 4 | 50% |
| United Kingdom | 1 | 13% |
| Unknown | 3 | 38% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 75% |
| Scientists | 2 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 2 | 4% |
| United States | 1 | 2% |
| Japan | 1 | 2% |
| Unknown | 48 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 15 | 29% |
| Researcher | 8 | 15% |
| Student > Bachelor | 7 | 13% |
| Professor > Associate Professor | 5 | 10% |
| Professor | 4 | 8% |
| Other | 10 | 19% |
| Unknown | 3 | 6% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 24 | 46% |
| Biochemistry, Genetics and Molecular Biology | 6 | 12% |
| Medicine and Dentistry | 3 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 6% |
| Computer Science | 2 | 4% |
| Other | 8 | 15% |
| Unknown | 6 | 12% |