Calcium as a modulator of the immediate-early gene cascade in neurons

doi:10.1016/0143-4160(88)90011-5

Cell Calcium

Volume 9, Issues 5–6, October–December 1988, Pages 303-311

https://doi.org/10.1016/0143-4160(88)90011-5 Get rights and content

Abstract

Increases in intraneuronal free calcium result in the rapid, transient, induction of the fos and jun proto-oncogenes. In PC12 cells, induction may be elicited either by membrane depolarization or by direct activation of voltage-dependent calcium channels with BAY K 8644 both of which provoke an influx of calcium. The calmodulin pathway appears to link the elevated intracellular calcium to gene induction. In the brain, c-fos and c-jun may be induced by elevated neuronal activity such as occurs during pentylenetetrazole (PTZ) seizures. The N-methyl-d-aspartate (NMDA) form of the glutamate receptor, which can directly gate calcium, plays a role in the induction of c-fos expression in PTZ seizures. In addition, NMDA can directly stimulate c-fos in the brain.

Fos and Jun form a noncovalent nucleoprotein complex that binds to the consensus recognition sequence of the AP-1 transcription factor. Thus in a larger picture we envisage Fos and Jun as members of a concerted stimulus-transcription coupling pathway that links alterations in external stimuli to long term adaptive responses. In this context Fos, Jun and the other immediate-early genes should be viewed as third messengers which are regulated by second messengers such as intracellular calcium.

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Citation Excerpt :
In neurons, the relationship between stimuli and gene regulation remains mesmerizingly inscrutable. In the mid 80’s, several groups made the observation that extracellular stimuli could trigger the expression of proto-oncogenes including c-Fos and c-Myc (also called Fos and Myc) in a variety of cell types [2–6]. Soon, several groups demonstrated that seizures and sensory stimuli induced Fos expression in the brain [7–9] and the field of activity-dependent gene regulation in neurons was born.
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Calcium as a modulator of the immediate-early gene cascade in neurons

Abstract

Cell

Cell

Cell

Cell

Trends in Neurosci.

Trends in Neurosci.

Mol. Brain Res.

Cell

Cell

Inositol trisphosphate and diacylglycerol: two interacting second messengers

Annu. Rev. Biochem.

Role of ion flux in the control of c-fos expression

Nature

Memories of fos

BioEssays

Analysis of Fos protein complexes and Fos-related antigens by high resolution two-dimensional gel electrophoresis

Oncogene

The fos oncogene

Expression of a set of growth-related immediate-early genes in BALBc 3T3 cells: coordinate regulation with c-fos and c-myc

Cloning of tetradecanoyl phorbol ester induced “primary response” sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant

Oncogene

Viral and cellular fos proteins are complexed with a 39,000 dalton protein

Mol. Cell. Biol.

Expression of a set of growth-related immediate-early genes in $BALB c$ 3T3 cells: coordinate regulation with c-fos and c-myc