Paper: Analytic study of the mutiple phosphorylation process

[Hide Cateau]

Dear All,

I would like to announce the availability of the following paper at my
web site:
http://brain.inf.eng.tamagawa.ac.jp/cateau/hide.index.html

Hideyuki Cateau and Shigeru Tanaka, Kinetic analysis of multisite
phosphorylation using analytic solutions to Michaelis-Menten
equations, J.Theor.Biol.(2002)217:1-14

This paper provides temporal progress curves of multiple
phosphorylation that occurs frequently in the intracellular signal
transduction pathway.  The temporal progress curves are given
analytically, so that they enable us to analyze the signal
transduction pathway quantitatively.


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Kinetic Analysis of Multisite Phosphorylation Using Analytic Solutions
to Michaelis-Menten Equations

Hideyuki Cateau and ShigeruTanaka

Laboratory for Visual Neurocomputing, RIKEN Brain Science Institute,
Hirosawa 2-1, Wako, Saitama 351-0198, Japan

Phosphorylation-induced expression or modulation of a functional
protein is a common signal in living cells. Many functional proteins
are phosphorylated at multiple sites and it is frequently observed
that phosphorylation at one site enhances or suppresses
phosphorylation at another site. Therefore, characterizing such
cooperative phosphorylation is important.

In this study, we determine a temporal progress curve of multisite
phosphorylation by analytically integrating the Michaelis-Menten
equations in time. Using this theoretical progress curve, we derive
the useful criterion that an intersection of two progress curves
implies the presence of cooperativity.  Experiments generally yield
noisy progress curves.  We fit the theoretical progress curves to
noisy progress curves containing 4% Gaussian noise in order to
determine the kinetics of the phosphorylation.  This fitting correctly
identifes the sites involved in cooperative phosphorylation.

(c) 2002 Elsevier Science Ltd. All rights reserved.

____________________________________________________________
Hideyuki Cateau
Core Research for the Evolutional
Science and Technology Program(CREST), JST
Lab. for mathematical information engineering,
Dept. Info-Communication Engineering,
Tamagawa Univ.
6-1-1 Tamagawa-Gakuen, Machida-shi, Tokyo 1948610, Japan
cateau at brain.inf.eng.tamagawa.ac.jp
http://brain.inf.eng.tamagawa.ac.jp/members.html
phone: +81-42-739-8434, fax:+81-42-739-7135
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