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A systems biology model of junctional localization and downstream signaling of the Ang-Tie signaling pathway.

Publication ,  Journal Article
Zhang, Y; Kontos, CD; Annex, BH; Popel, AS
Published in: NPJ Syst Biol Appl
August 20, 2021

The Ang-Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang-Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang-Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang-Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2's response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1's junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2's agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.

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Published In

NPJ Syst Biol Appl

DOI

EISSN

2056-7189

Publication Date

August 20, 2021

Volume

7

Issue

1

Start / End Page

34

Location

England

Related Subject Headings

  • Systems Biology
  • Signal Transduction
  • Receptor, TIE-2
  • Endothelial Cells
  • Biological Phenomena
  • 3102 Bioinformatics and computational biology
 

Citation

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Zhang, Y., Kontos, C. D., Annex, B. H., & Popel, A. S. (2021). A systems biology model of junctional localization and downstream signaling of the Ang-Tie signaling pathway. NPJ Syst Biol Appl, 7(1), 34. https://doi.org/10.1038/s41540-021-00194-6
Zhang, Yu, Christopher D. Kontos, Brian H. Annex, and Aleksander S. Popel. “A systems biology model of junctional localization and downstream signaling of the Ang-Tie signaling pathway.NPJ Syst Biol Appl 7, no. 1 (August 20, 2021): 34. https://doi.org/10.1038/s41540-021-00194-6.
Zhang Y, Kontos CD, Annex BH, Popel AS. A systems biology model of junctional localization and downstream signaling of the Ang-Tie signaling pathway. NPJ Syst Biol Appl. 2021 Aug 20;7(1):34.
Zhang, Yu, et al. “A systems biology model of junctional localization and downstream signaling of the Ang-Tie signaling pathway.NPJ Syst Biol Appl, vol. 7, no. 1, Aug. 2021, p. 34. Pubmed, doi:10.1038/s41540-021-00194-6.
Zhang Y, Kontos CD, Annex BH, Popel AS. A systems biology model of junctional localization and downstream signaling of the Ang-Tie signaling pathway. NPJ Syst Biol Appl. 2021 Aug 20;7(1):34.

Published In

NPJ Syst Biol Appl

DOI

EISSN

2056-7189

Publication Date

August 20, 2021

Volume

7

Issue

1

Start / End Page

34

Location

England

Related Subject Headings

  • Systems Biology
  • Signal Transduction
  • Receptor, TIE-2
  • Endothelial Cells
  • Biological Phenomena
  • 3102 Bioinformatics and computational biology