1. Angiopoietin-Tie Signaling Pathway in Endothelial Cells: A Computational Model
- Author
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Aleksander S. Popel, Christopher D. Kontos, Brian H. Annex, and Yu Zhang
- Subjects
0301 basic medicine ,Angiogenesis ,Bioinformatics ,Systems biology ,Regulator ,02 engineering and technology ,Biology ,Systemic inflammation ,TIE1 ,Article ,Angiopoietin ,03 medical and health sciences ,0502 economics and business ,medicine ,Tie signaling pathway ,050207 economics ,lcsh:Science ,050208 finance ,Multidisciplinary ,05 social sciences ,Cancer ,Cell Biology ,Biological Sciences ,021001 nanoscience & nanotechnology ,medicine.disease ,Angiopoietin receptor ,3. Good health ,Cell biology ,030104 developmental biology ,biology.protein ,lcsh:Q ,medicine.symptom ,Signal transduction ,0210 nano-technology - Abstract
Summary The angiopoietin-Tie signaling pathway is an important vascular signaling pathway involved in angiogenesis, vascular stability, and quiescence. Dysregulation in the pathway is linked to the impairments in vascular function associated with many diseases, including cancer, ocular diseases, systemic inflammation, and cardiovascular diseases. The present study uses a computational signaling pathway model validated against experimental data to quantitatively study various mechanistic aspects of the angiopoietin-Tie signaling pathway, including receptor activation, trafficking, turnover, and molecular mechanisms of its regulation. The model provides mechanistic insights into the controversial role of Ang2 and its regulators vascular endothelial protein tyrosine phosphatase (VE-PTP) and Tie1 and predicts synergistic effects of inhibition of VE-PTP, Tie1, and Tie2 cleavage on enhancing the vascular protective actions of Tie2., Graphical Abstract, Highlights • Mechanistically detailed computational model of the angiopoietin-Tie pathway • Receptor internalization dynamics modulate effectiveness of VE-PTP • Inhibition of VE-PTP, Tie1, and Tie2 shedding synergistically enhances Tie2 activation • Tie1 silencing modulates the effectiveness of inhibiting VE-PTP and Tie2 shedding, Biological Sciences; Cell Biology; Bioinformatics
- Published
- 2019