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CREB/CBP and SRE‐interacting transcriptional regulators are fast on–off switches: duration of calcium transients specifies the magnitude of transcriptional responses
Author(s) -
Chawla Sangeeta,
Bading Hilmar
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00645.x
Subject(s) - creb , microbiology and biotechnology , calcium , camk , kinase , voltage dependent calcium channel , biology , calcium signaling , transcription factor , chemistry , signal transduction , neuroscience , protein kinase a , medicine , biochemistry , autophosphorylation , gene
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.