Kolodkin, AN, Bruggeman, FJ, Plant, N orcid.org/0000-0003-4332-8308 et al. (7 more authors) (2010) Design principles of nuclear receptor signaling: how complex networking improves signal transduction. Molecular Systems Biology, 6 (1). Article number 446. ISSN 1744-4292
Abstract
The topology of nuclear receptor (NR) signaling is captured in a systems biological graphical notation. This enables us to identify a number of ‘design’ aspects of the topology of these networks that might appear unnecessarily complex or even functionally paradoxical. In realistic kinetic models of increasing complexity, calculations show how these features correspond to potentially important design principles, e.g.: (i) cytosolic ‘nuclear’ receptor may shuttle signal molecules to the nucleus, (ii) the active export of NRs may ensure that there is sufficient receptor protein to capture ligand at the cytoplasmic membrane, (iii) a three conveyor belts design dissipating GTP‐free energy, greatly aids response, (iv) the active export of importins may prevent sequestration of NRs by importins in the nucleus and (v) the unspecific nature of the nuclear pore may ensure signal‐flux robustness. In addition, the models developed are suitable for implementation in specific cases of NR‐mediated signaling, to predict individual receptor functions and differential sensitivity toward physiological and pharmacological ligands.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | (c) 2010 EMBO and Macmillan Publishers Limited. Molecular Systems Biology is an open-access journal published by European Molecular Biology Organization and Nature Publishing group. This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License. |
Keywords: | biochemical network; kinetic model; nuclear receptor; signaling; systems biology |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Jul 2019 09:36 |
Last Modified: | 10 Jul 2019 09:36 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1038/msb.2010.102 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:125254 |
Download
Licence: CC-BY-NC-SA 3.0