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Signalling by protein phosphatases and drug development: a systems‐centred view
Author(s) -
Nguyen Lan K.,
Matallanas David,
Croucher David R.,
von Kriegsheim Alexander,
Kholodenko Boris N.
Publication year - 2013
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.1742-4658.2012.08522.x
Subject(s) - signalling , phosphatase , kinase , function (biology) , signal transduction , microbiology and biotechnology , biology , phosphorylation , computational biology , biochemistry
Protein modification cycles catalysed by opposing enzymes, such as kinases and phosphatases, form the backbone of signalling networks. Although, historically, kinases have been at the research forefront, a systems‐centred approach reveals predominant roles for phosphatases in controlling the network response times and spatio‐temporal profiles of signalling activities. Emerging evidence suggests that phosphatase kinetics are critical for network function and cell‐fate decisions. Protein phosphatases operate as both immediate and delayed regulators of signal transduction, capable of attenuating or amplifying signalling. This versatility of phosphatase action emphasizes the need for systems biology approaches to understand cellular signalling networks and predict the cellular outcomes of combinatorial drug interventions.