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Effect of the MAPK cascade structure, nuclear translocation and regulation of transcription factors on gene expression

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Title Effect of the MAPK cascade structure, nuclear translocation and regulation of transcription factors on gene expression
 
Creator MUTALIK, VIVEK K
VENKATESH, KV
 
Subject mapk cascade
switch-like responses
ultrasensitivity
systems biology
theoretical modeling
regulatory design principles
 
Description The mitogen activated protein kinase (MAP kinase) cascade system represents a highly conserved prototype of signal transduction by enzyme cascades. One of the best-studied properties of the MAPK system is its ability to convert graded input stimulus to switch-like all-or-none responses. Previous theoretical studies have centered on quantifying dual phosphorylated MAPK as a final output response and have not incorporated its influence on the regulation of gene expression. The main objective of the current work is to understand the regulatory effect of positive feedback loop embedded in the MAPK cascade, nuclear translocation of active MAPK, phosphorylation and activation of nuclear target proteins on the regulation of specific gene expression. To achieve this objective, we have simulated the MAPK cascade system, which resembles Hog1p activation pathway in yeast, at steady state. Thus, the input signal to the MAPK system is correlated with gene expression as a final system-level output response. The steady state simulation results suggest that other than regulating the signal propagation through cascades, the nuclear translocation of activated MAPK and subsequent regulation of gene expression represent one of the key modes to control the threshold level of response. This work proposes that, it is essential to consider the compartmental distributions of signaling species and the corresponding regulatory mechanisms of gene expression to study the system-level performance of signaling modules such as the MAPK cascade. Such an analysis will relate the extracellular cues to the final phenotypic response by capturing the mechanistic details of the signaling pathway.
 
Publisher Elsevier
 
Date 2009-03-19T05:11:55Z
2011-11-25T19:32:19Z
2011-12-26T13:07:35Z
2011-12-27T05:55:38Z
2009-03-19T05:11:55Z
2011-11-25T19:32:19Z
2011-12-26T13:07:35Z
2011-12-27T05:55:38Z
2006
 
Type Article
 
Identifier Biosystems 85(2), 144-157
0303-2647
http://dx.doi.org/10.1016/j.biosystems.2006.01.001
http://hdl.handle.net/10054/992
http://dspace.library.iitb.ac.in/xmlui/handle/10054/992
 
Language en