PT  - JOURNAL ARTICLE
AU  - Susanne Roth
AU  - Boris N Kholodenko
AU  - M J Smit
AU  - Frank J Bruggeman
TI  - G Protein-Coupled Receptor Signalling Networks from a Systems Perspective
AID  - 10.1124/mol.115.100057
DP  - 2015 Jul 10
TA  - Molecular Pharmacology
PG  - mol.115.100057
4099  - http://molpharm.aspetjournals.org/content/early/2015/07/10/mol.115.100057.short
4100  - http://molpharm.aspetjournals.org/content/early/2015/07/10/mol.115.100057.full
AB  - The signal-transduction network of a mammalian cell integrates internal and external cues in order to initiate adaptive responses. Amongst the cell-surface receptors are the G protein-coupled receptors (GPCRs) that have remarkable signal-integrating capabilities. Binding of extracellular signals stabilises intracellular-domain conformations that selectively activate intracellular proteins. Hereby, multiple signalling routes are activated simultaneously to degrees that are signal-combination dependent. Systems-biology studies indicate that signalling networks have emergent processing capabilities that go far beyond those of single proteins. Such networks are spatiotemporally organised and capable of gradual, oscillatory, all-or-none and subpopulation-generating responses. Protein-protein interactions, generating feedback and feedforward circuitry, are generally required for these spatiotemporal phenomena. Understanding of information processing by signalling networks therefore requires network theories in addition to biochemical and biophysical concepts. Here we review some of the key signalling-systems behaviours that have been discovered recurrently across signalling networks. We emphasise the role of GPCRs, so far under appreciated receptors in systems-biology research.