CREB/CBP and SRE-interacting transcriptional regulators are fast on-off switches: duration of calcium transients specifies the magnitude of transcriptional responses

S Chawla, H Bading

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)849-58
Number of pages10
JournalJournal of Neurochemistry
Issue number4
Publication statusPublished - 2001


  • Animals
  • Brain-Derived Neurotrophic Factor
  • CREB-Binding Protein
  • Calcium Channel Agonists
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Calcium Signaling
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Nucleus
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein
  • Gene Expression
  • Genes, Reporter
  • Hippocampus
  • MAP Kinase Signaling System
  • Mice
  • Neurons
  • Nuclear Proteins
  • Phosphorylation
  • Pituitary Gland
  • RNA, Messenger
  • Serum Response Element
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic
  • Transfection

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