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• W1545537075 abstract "Transient increases in the intracellular calcium concentration, which are associated with electrical activation of neurones, control synapse-to-nucleus communication. Calcium signals differ in time and space but it is unclear exactly how this translates into stimulus-specific gene expression. Analysis of transcription induced by calcium transients with defined durations revealed that the evoked genomic responses, unlike those following neurotrophin exposure, are not all-or-none but graded events. The CRE-binding protein CREB, its coactivator CREB-binding protein (CBP), and SRE-interacting transcriptional regulators are fast on–off switches: their activities are induced by short-lasting calcium signals, remain active for the duration of the signal and are rapidly shut-off after calcium concentrations have returned to basal levels. CREB is switched on by a fast, nuclear calmodulin (CaM) kinase-dependent mechanism that mediates CREB phosphorylation on serine 133 within 30 s of calcium entry. The second calcium-activated route to CREB involves the MAP kinase/extracellular signal-regulated kinase (ERK1/2) cascade. This pathway can be triggered by brief, 30–60 s calcium transients. ERK1/2 activity peaks several minutes after calcium entry and can outlast the calcium transient. The shut-off of CREB and ERK1/2 involves rapid dephosphorylation of their activator sites. These properties of transcription factors and their regulating kinases and phosphatases provide a mechanism through which the duration of calcium signals specifies the magnitude of the transcriptional response. The decoding of temporal features of calcium transients is likely to contribute to impulse-specific gene expression." @default.
• W1545537075 created "2016-06-24" @default.
• W1545537075 creator A5005468753 @default.
• W1545537075 creator A5075463026 @default.
• W1545537075 date "2008-07-07" @default.
• W1545537075 modified "2023-10-16" @default.
• W1545537075 title "CREB/CBP and SRE-interacting transcriptional regulators are fast on-off switches: duration of calcium transients specifies the magnitude of transcriptional responses" @default.
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• W1545537075 doi "https://doi.org/10.1046/j.1471-4159.2001.00645.x" @default.
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