Document Detail


Signaling cascades as cellular devices for spatial computations.
MedLine Citation:
PMID:  18283462     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Signaling networks usually include protein-modification cycles. Cascades of such cycles are the backbones of multiple signaling pathways. Protein gradients emerge from the spatial separation of opposing enzymes, such as kinases and phosphatases, or guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) for GTPase cycles. We show that different diffusivities of an active protein form and an inactive form leads to spatial gradients of protein abundance in the cytoplasm. For a cascade of cycles, using a discrete approximation of the space, we derive an analytical expression for the spatial gradients and show that it converges to an exact solution with decreasing the size of the quantization. Our results facilitate quantitative analysis of the dependence of spatial gradients on the network topology and reaction kinetics. We demonstrate how different cascade designs filter and process the input information to generate precise, complex spatial guidance for multiple GTPase effector processes. Thus, protein-modification cascades may serve as devices to compute complex spatial distributions of target proteins within intracellular space.
Authors:
Jörg Stelling; Boris N Kholodenko
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-02-19
Journal Detail:
Title:  Journal of mathematical biology     Volume:  58     ISSN:  0303-6812     ISO Abbreviation:  J Math Biol     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-10-10     Completed Date:  2009-03-31     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502105     Medline TA:  J Math Biol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  35-55     Citation Subset:  IM    
Affiliation:
Institute of Computational Science and Swiss Institute of Bioinformatics, ETH Zurich, 8092, Zurich, Switzerland. joerg.stelling@inf.ethz.ch
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MeSH Terms
Descriptor/Qualifier:
Computer Simulation
GTPase-Activating Proteins / metabolism*
Guanine Nucleotide Exchange Factors / metabolism*
Models, Biological*
Signal Transduction
Grant Support
ID/Acronym/Agency:
GM059570/GM/NIGMS NIH HHS; R01 GM059570-08A1/GM/NIGMS NIH HHS; R33 HL088283-02/HL/NHLBI NIH HHS; R33HL088283/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/GTPase-Activating Proteins; 0/Guanine Nucleotide Exchange Factors
Comments/Corrections

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