Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB

Sheng, Morgan; McFadden, Grant; Greenberg, Michael E.

doi:10.1016/0896-6273(90)90115-v

Cited by 1,016 publications

(604 citation statements)

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“…Nor was there a correlation between c-fos mRNA levels and phosphorylation of CREB, the cyclic AMP response element-binding protein on which Ca 2ϩ and cyclic AMP signals converge, leading to activation of c-fos transcription (58). Indeed, as shown in Fig.…”

Section: Resultsmentioning

confidence: 95%

“…Basal contraction of stressed collagen matrices results in Ca 2ϩ uptake and an increase in cyclic AMP (26,27,38), and Ca 2ϩ and cyclic AMP have been implicated in the stimulation of c-fos transcription through the cyclic AMP response element (58). Therefore, we tested the possibility that Ca 2ϩ and cyclic AMP are important for c-fos stimulation during contraction.…”

Section: Resultsmentioning

confidence: 99%

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Increased c-fos mRNA Expression By Human Fibroblasts Contracting Stressed Collagen Matrices

Rosenfeldt

Lee

Grinnell

1998

Molecular and Cellular Biology

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We studied early changes in gene expression during fibroblast contraction of stressed collagen matrices. The level of c-fos mRNA increased dramatically and peaked 50 to 60 min after matrix contraction was initiated. This response did not require serum and could not be accounted for simply by disruption of the actin cytoskeleton. Increased c-fos mRNA levels required Ca 2؉ influx but not the cyclic AMP or extracellular signal-regulated kinase (ERK 1/2) signaling pathways, both of which are activated when fibroblasts contract stressed collagen matrices. The levels of two other immediate-early genes, fosb and c-jun, also increased transiently after fibroblast contraction, whereas the levels of fra-1, fra-2, c-myc, and the transcription factor NF-B remained the same, indicating that fibroblast contraction caused changes in a selective group of genes. The increase in c-fos mRNA during contraction of stressed collagen matrices may reflect a unique role for c-fos in mechanoregulated events at the end of wound repair.Mechanical force influences cell function in animal and plant tissues (6,11,30,67). For instance, increased mechanical load, such as fluid flow over endothelial cells or tension applied to muscle cells, has been shown to result in cell proliferation or hypertrophy (15, 64). During wound repair, mechanical force within the wound tissue pulls the wound edges closer together, which in pathological cases results in scarring and loss of function (29, 52). Wound contraction is believed to be mediated by fibroblasts as they go through a cycle of migration, proliferation, contraction, and regression (13,40).Fibroblasts cultured in collagen matrices have been used as an in vitro model for wound contraction (3,20). In this model, cells reorganize the extracellular matrix through migratory and contractile activities (3, 25), resulting in formation of a dense, tissue-like structure. The fibroblast phenotype that develops during collagen matrix reorganization differs dramatically depending upon whether collagen matrices are floating in medium or attached to a rigid support. After reorganization of attached matrices, the cells resemble proliferating fibroblasts of wound tissue under mechanical stress and are characterized by polarized morphology, prominent stress fibers, and fibronexus junctions (23,37,45,62). Cells in attached collagen matrices exert force on the matrix similar to that observed in contracting skin wounds (12, 34). After reorganization of floating matrices, on the other hand, cells resemble nondividing fibroblasts of resting dermis or scar tissue in a state of mechanical equilibrium and are characterized by isometric (stellate) cell morphology and cytoskeletal meshwork (3, 4).We have combined the attached and floating models to study the regulatory events associated with the transition of fibroblasts from mechanically stressed to mechanically equilibrated conditions (stress-relaxation) such as occurs by the end of wound repair. Initially, fibroblasts are cultured in attached collagen matrices until mechan...

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Increased c-fos mRNA Expression By Human Fibroblasts Contracting Stressed Collagen Matrices

Rosenfeldt

Lee

Grinnell

1998

Molecular and Cellular Biology

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“…CREB is activated in neurons in response to trans‐synaptic signaling and regulates the expression of genes that are essential for adaptive neuronal responses, as well as more complex neural functions, such as learning and memory (Alberini & Chen, 2012). CREB target genes include immediate‐early genes, such as c‐fos (Sheng et al ., 1990), and others important for synaptic function, such as BDNF (Shieh et al ., 1998) and neuronal nitric oxide synthase (nNOS) (Sasaki et al ., 2000). CREB activation is induced through ser‐133 phosphorylation mediated by a variety of kinases, including the PI3K‐activated AKT (reviewed in Lonze & Ginty, 2002).…”

Section: Introductionmentioning

confidence: 99%

Amyloid Beta monomers regulate cyclic adenosine monophosphate response element binding protein functions by activating type‐1 insulin‐like growth factor receptors in neuronal cells

et al. 2017

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SummaryAlzheimer's disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of β‐amyloid (Aβ), and neuronal loss. The self‐association of Aβ monomers into soluble oligomers seems to be crucial for the development of neurotoxicity (J. Neurochem., 00, 2007 and 1172). Aβ oligomers have been suggested to compromise neuronal functions in AD by reducing the expression levels of the CREB target gene and brain‐derived neurotrophic factor (BDNF) (J. Neurosci., 27, 2007 and 2628; Neurobiol. Aging, 36, 2015 and 20406 Mol. Neurodegener., 6, 2011 and 60). We previously reported a broad neuroprotective activity of physiological Aβ monomers, involving the activation of type‐1 insulin‐like growth factor receptors (IGF‐IRs) (J. Neurosci., 29, 2009 and 10582, Front Cell Neurosci., 9, 2015 and 297). We now provide evidence that Aβ monomers, by activating the IGF‐IR‐stimulated PI3‐K/AKT pathway, induce the activation of CREB in neurons and sustain BDNF transcription and release.

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“…Our results, therefore, are more consistent with the first mechanism. However, because c-fos mRNA transcription may be autoregulated [61], the inhibition of Fos protein synthesis may activate c-fos mRNA transcription, causing an increase in newly transcribed c-fos mRNA. Whether c-fos mRNA content can be maintained (and compensate for degraded c-fos mRNA) by such a mechanism remains to be determined.…”

mentioning

confidence: 99%

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

Liu

Salminen

et al. 1994

Annals of Neurology

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Activation of c-fos, an immediate early gene, and the subsequent expression of the Fos protein have been noted following focal cerebral ischemia. Fos and Jun form a heterodimer as activator protein 1 (AP-1), which transregulates the expression of several genes. To study the postischemic events related to c-fos expression, we suppressed the expression of c-fos by intraventricular infusion of an antisense Oligodeoxynucleotide (anti-rncfosr 115 ) of c-fos mRNA. The effectiveness of antirncfosr 115 was confirmed first by its capability to block in vitro c-fos mRNA translation. In vivo, after intraventricular infusion of 32 P-labeled anti-rncfosr 115 , the oligodeoxynucleotide was internalized within 6 hours and detectable also in the nucleic acids fraction up to 41 hours. Treatment of the recovered nucleic acids with RNase H separated the labeled Oligodeoxynucleotide from the nucleic acid fraction, indicating an association of the antisense Oligodeoxynucleotide and cellular RNA after uptake. When focal cerebral ischemia was induced 16 hours after the infusion of antirncfosr 115 , the postischemic increase in Fos expression and AP-1 binding activity were suppressed. Specificity of the effect of anti-rncfosr 115 was suggested by its failure to suppress the DNA binding activity of nuclear cyclic AMP response elements. These results support the hypothesis that increased AP-1 binding activity following focal cerebral ischemia is dependent on Fos expression and can be inhibited in vivo by antisense c-fos oligodeoxynucleotides.The molecular events of brain adaptation to injury that may underlie functional recovery after stroke remain largely undefined. Recent observations of altered gene expression in ischemic brain using animal stroke models have opened new avenues for exploration of the biochemical cascades after stroke [1][2][3][4][5][6][7][8][9][10][11]. These postischemic events include an increase in extracellular excitatory amino acid neurotransmitters such as glutamate. Glutamate receptor-mediated activation of phospholipases and protein kinases results in the alteration of nuclear regulatory processes, including the expression of immediate early genes such as c-fos, junB, and c-jun [5,12]. The Fos, Jun, and JunB proteins have been shown to form activator protein 1 (AP-1) through a conserved dimerization domain, i.e., the leucine zipper [13]. Transcription regulator AP-1 protein binds a specific DNA motif and is believed to transactivate the expression of a number of late effector genes [14][15][16][17][18][19]. In the ischemic brain, we have previously demonstrated an increase in AP-1 binding activity [9]. A number of genes that bear neurotrophic properties may be regulated by transcription regulator AP-1. These genes, such as heat shock protein [1,4,[19][20][21][22], amyloid [23], neurotrophins [7], and protein tyrosine kinase receptor trkB [24], have been shown to be induced following cerebral ischemia. The causal relationship between the Fos/Jun-AP-1 cascade and the subsequent expression of the late e...

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Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB

Cited by 1,016 publications

References 50 publications

Increased c-fos mRNA Expression By Human Fibroblasts Contracting Stressed Collagen Matrices

Increased c-fos mRNA Expression By Human Fibroblasts Contracting Stressed Collagen Matrices

Amyloid Beta monomers regulate cyclic adenosine monophosphate response element binding protein functions by activating type‐1 insulin‐like growth factor receptors in neuronal cells

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

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