How quantitative measures unravel design principles in multi-stage phosphorylation cascades

Abstract:

We investigate design principles of linear multi-stage phosphorylation cascades by using quantitative measures for signaling time, signal duration and signal amplitude. We compare alternative pathway structures by varying the number of phosphorylations and the length of the cascade. We show that a model for a weakly activated pathway does not reflect the biological context well, unless it is restricted to certain parameter combinations. Focusing therefore on a more general model, we compare alternative structures with respect to a multivariate optimization criterion. We test the hypothesis that the structure of a linear multi-stage phosphorylation cascade is the result of an optimization process aiming for a fast response, defined by the minimum of the product of signaling time and signal duration. It is then shown that certain pathway structures minimize this criterion. Several popular models of MAPK cascades form the basis of our study. These models represent different levels of approximation, which we compare and discuss with respect to the quantitative measures.

SEEK ID: https://fairdomhub.org/publications/54

PubMed ID: 18573504

Projects: BaCell-SysMO

Journal: J. Theor. Biol.

Citation:

Date Published: 6th Sep 2007

Authors: Simone Frey, Thomas Millat, Stefan Hohmann, Olaf Wolkenhauer

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Created: 20th Aug 2010 at 15:50

Last updated: 5th Oct 2010 at 09:35

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