Premium
Principles behind the multifarious control of signal transduction
Author(s) -
Hornberg Jorrit J.,
Bruggeman Frank J.,
Binder Bernd,
Geest Christian R.,
de Vaate A. J. Marjolein Bij,
Lankelma Jan,
Heinrich Reinhart,
Westerhoff Hans V.
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1432-1033.2004.04404.x
Subject(s) - phosphatase , signal (programming language) , signal transduction , mapk/erk pathway , amplitude , duration (music) , kinase , phosphorylation , microbiology and biotechnology , physics , biology , computer science , acoustics , optics , programming language
General and simple principles are identified that govern signal transduction. The effects of kinase and phosphatase inhibition on a MAP kinase pathway are first examined in silico . Quantitative measures for the control of signal amplitude, duration and integral strength are introduced. We then identify and prove new principles, such that total control on signal amplitude and on final signal strength must amount to zero, and total control on signal duration and on integral signal intensity must equal −1. Collectively, kinases control amplitudes more than duration, whereas phosphatases tend to control both. We illustrate and validate these principles experimentally: (a) a kinase inhibitor affects the amplitude of EGF‐induced ERK phosphorylation much more than its duration and (b) a phosphatase inhibitor influences both signal duration and signal amplitude, in particular long after EGF administration. Implications for the cellular decision between growth and differentiation are discussed.