title: Signalling by protein phosphatases and drug development: a systems-centred view.
abstract: 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.
authors.affiliation: Systems Biology Ireland, University College Dublin, Belfield, Ireland.
authors.forename: Lan K
authors.initials: LK
authors.lastname: Nguyen
authors.forename: David
authors.initials: D
authors.lastname: Matallanas
authors.forename: David R
authors.initials: DR
authors.lastname: Croucher
authors.forename: Alexander
authors.initials: A
authors.lastname: von Kriegsheim
authors.forename: Boris N
authors.initials: BN
authors.lastname: Kholodenko
mesh_terms: D055808:Drug Discovery / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D049490:Systems Biology / Q000379:methods
chemical_list: D004791:Enzyme Inhibitors; D010749:Phosphoprotein Phosphatases