Imperial College London
Portrait Picture

DrVahidShahrezaei

Faculty of Natural Sciences, Department of Mathematics

Reader in Biomathematics
 
 
 
//

Contact

 

+44 (0)20 7594 8516v.shahrezaei Website

 
 
//

Location

 

301BSir Ernst Chain BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Szomolay:2012:10.1186/1752-0509-6-26,
author = {Szomolay, B and Shahrezaei, V},
doi = {10.1186/1752-0509-6-26},
journal = {BMC Systems Biology},
pages = {1--14},
title = {Bell-shaped and ultrasensitive dose-response in phosphorylation-dephosphorylation cycles: the role of kinase-phosphatase complex formation},
url = {http://dx.doi.org/10.1186/1752-0509-6-26},
volume = {6},
year = {2012}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundPhosphorylation-dephosphorylation cycles (PDCs) mediated by kinases and phosphatases are common in cellular signalling. Kinetic modelling of PDCs has shown that these systems can exhibit a variety of input-output (dose-response) behaviors including graded response, ultrasensitivity and bistability. In addition to proteins, there are a class of lipids known as phosphoinositides (PIs) that can be phosphorylated. Experimental studies have revealed the formation of an antagonistic kinase-phosphatase complex in regulation of phosphorylation of PIs. However, the functional significance of this type of complex formation is not clear.ResultsWe first revisit the basic PDC and show that partial asymptotic phosphorylation of substrate limits ultrasensitivity. Also, substrate levels are changed one can obtain non-monotonic bell-shaped dose-response curves over a narrow range of parameters. Then we extend the PDC to include kinase-phosphatase complex formation. We report the possibility of robust bell-shaped dose-response for a specific class of the model with complex formation. Also, we show that complex formation can produce ultrasensitivity outside the Goldbeter-Koshland zero-order ultrasensitivity regime through a mechanism similar to competitive inhibition between an enzyme and its inhibitor.ConclusionsWe conclude that the novel PDC module studied here exhibits new dose-response behaviour. In particular, we show that the bell-shaped response could result in transient phosphorylation of substrate. We discuss the relevance of this result in the context of experimental observations on PI regulation in endosomal trafficking.
AU  - Szomolay,B
AU  - Shahrezaei,V
DO  - 10.1186/1752-0509-6-26
EP  - 14
PY  - 2012///
SN  - 1752-0509
SP  - 1
TI  - Bell-shaped and ultrasensitive dose-response in phosphorylation-dephosphorylation cycles: the role of kinase-phosphatase complex formation
T2  - BMC Systems Biology
UR  - http://dx.doi.org/10.1186/1752-0509-6-26
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000309120300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-6-26
UR  - http://hdl.handle.net/10044/1/76328
VL  - 6
ER  -
Download