Brain-derived neurotrophic factor-, epidermal growth factor-, or A-Raf-induced growth of HaCaT keratinocytes requires extracellular signal-regulated kinase

Rößler, Oliver G.; Thiel, Gerald

doi:10.1152/ajpcell.00301.2003

Cited by 25 publications

(21 citation statements)

References 43 publications

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“…In fact, induction of Egr-1 gene transcription was monitored in many cell types in response to mitogens, and a direct role of Egr-1 in controlling proliferation has been proposed for astrocytes, glioma cells, glomerular mesangial cells, keratinocytes and T-cells (Perez-Castillo et al, 1993;Biesiada et al, 1996;Hofer et al, 1996;Kaufmann and Thiel, 2002;Rössler and Thiel, 2004). Egr-1 biosynthesis is strongly stimulated by activation of ERK , the protein kinase that is activated by mitogens.…”

Section: Discussionmentioning

confidence: 99%

Epidermal-growth-factor-induced proliferation of astrocytes requires Egr transcription factors

Mayer

Rößler

Endo

et al. 2009

Journal of Cell Science

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Stimulation of astrocytes with epidermal growth factor (EGF) induced proliferation and triggered the biosynthesis of the transcription factor Egr-1, involving the activation of the extracellular signal-regulated protein kinase (ERK) signaling pathway. No differences in the proliferation rate of astrocytes prepared from wild-type or Egr-1-deficient mice were detected. However, expression of a dominant-negative mutant of Egr-1 that interfered with DNA-binding of all Egr proteins prevented EGF-induced proliferation of astrocytes. Site-directed mutagenesis of two crucial cysteine residues within the zinc finger DNA-binding domain revealed that DNA-binding of the Egr-1 mutant was essential to inhibit proliferation of EGF-stimulated astrocytes. Expression of NAB2 (a negative co-regulator of Egr-1, Egr-2 and Egr-3) or a dominant-negative mutant of Elk-1 (a key regulator of Egr-1 biosynthesis) abolished EGF-induced proliferation of astrocytes. Chromatin immunoprecipitation experiments showed that Egr-1, Egr-2 and Egr-3 bound to the gene expressing basic fibroblast growth factor (bFGF) in EGF-stimulated astrocytes. Egr-2 and Egr-3 also interacted with the bFGF gene in EGF-stimulated astrocytes prepared from Egr-1-deficient mice, indicating that loss of Egr-1 is compensated by other Egr proteins. Together, these data show that Egr transcription factors are essential for conversion of the mitogenic signal of EGF into a proliferative response.

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Section: Discussionmentioning

confidence: 99%

Epidermal-growth-factor-induced proliferation of astrocytes requires Egr transcription factors

Mayer

Rößler

Endo

et al. 2009

Journal of Cell Science

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“…These data were corroborated by experiments involving HaCaT keratinocytes expressing the catalytic domain of A-Raf as a fusion protein with the ligand binding domain of the murine estrogen receptor (HaCaT-⌬ARaf:ER cells). Addition of 4OHT leads to an enhancement of A-Raf protein kinase activity and to a selective activation of the ERK signaling pathway (Rössler and Thiel, 2004). Figure 5B shows that conditional activation of the ERK signaling pathway in HaCaT keratinocytes expressing a ⌬ARaf-estrogen receptor fusion protein induced expression of Egr-1, a zinc finger transcription factor, but not of ATF3 as a result of 4OHT treatment.…”

Section: Thapsigargin-induced Signaling In Keratinocytes 869mentioning

confidence: 97%

Thapsigargin Induces Expression of Activating Transcription Factor 3 in Human Keratinocytes Involving Ca2+ Ions and c-Jun N-Terminal Protein Kinase

Spohn

Rößler²,

Philipp³

et al. 2010

Molecular Pharmacology

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Thapsigargin is a specific inhibitor of the sarco/endoplasmic reticulum Ca 2ϩ ATPase of the endoplasmic reticulum. Here, we show that stimulation of human HaCaT keratinocytes with nanomolar concentrations of thapsigargin triggers expression of activating transcription factor (ATF) 3, a basic-region leucin zipper transcription factor. ATF3 expression was also up-regulated in thapsigargin-stimulated glioma cells, hepatoma cells, retinal pigment epithelial cells, and airway epithelial cells. Thapsigargin-induced up-regulation of ATF3 expression in keratinocytes was attenuated by BAPTA-acetoxymethyl ester or by expression of the Ca 2ϩ -binding protein parvalbumin in the cytosol of HaCaT cells but not by a panel of pharmacological agents that chelate extracellular Ca 2ϩ (EGTA) or inhibit either ryanodine receptors (dantrolene) or voltage-gated Ca 2ϩ channels (nifedipine). Hence, elevated levels of intracellular Ca 2ϩ , released from intracellular stores, are essential for the effect of thapsigargin on the biosynthesis of ATF3. The thapsigargininduced signaling pathway was blocked by expression of either mitogen-activated protein kinase phosphatase-1 or -5. Experiments involving pharmacological and genetic tools revealed the importance of c-Jun N-terminal protein kinase (JNK) within the signaling cascade, whereas inhibition of extracellular signal-regulated protein kinase or p38 protein kinase did not attenuate thapsigargin-induced expression of ATF3. Functional studies showed that treatment of HaCaT keratinocytes with thapsigargin led to a 2-fold induction of caspase-3/7 activity. The up-regulation of caspase-3/7 activity in thapsigargin-stimulated HaCaT cells was attenuated by inhibition of JNK. Together, these data show that stimulation of HaCaT cells with thapsigargin induces a specific signaling pathway in keratinocytes involving activation of JNK, biosynthesis of ATF3, and up-regulation of caspase-3/7 activity.

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“…HaCaT keratinocytes were kindly provided by N. E. Fusenig, Deutsches Krebsforschungszentrum, Heidelberg, Germany. SH-SY5Y, HaCaT, and 293T cells were cultured as described (11)(12)(13). For differentiation, one million HNSC.100 neural stem cells were seeded in 100-mm plates for 24 h. The cells were washed with phosphate-buffered saline and incubated in culture medium lacking EGF and bFGF to initiate differentiation.…”

Section: Methodsmentioning

confidence: 99%

Transcription of Genes Encoding Synaptic Vesicle Proteins in Human Neural Stem Cells

Ekici

Hohl

Schuit

et al. 2008

Journal of Biological Chemistry

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Neural stem cells are characterized by their self-renewal ability and their capacity to differentiate into neurons, astrocytes, and oligodendrocytes, the major cell types of the central nervous system. Neural stem cells have been isolated from murine brain tissue, in particular from the subventricular zone or the subgranular layer of the hippocampus, i.e. brain regions exhibiting neurogenesis in the adult. Following dissection of the tissue, the dissociated cells are cultured in the presence of the mitogens epidermal growth factor (EGF) 2 and bFGF, giving rise to a mixed population of neural progenitor and stem cells (1). The use of neural stem cells as a cellular model to analyze differentiation processes requires the generation of a pure population of neural stem cells in a large enough quantity. This is, in particular for human neural stem cells, no easy task. It is in general difficult to get a reasonable number of human stem cells that maintain a stable phenotype during growth. Therefore, immortalized neural stem cell lines have been established that provide cells that can be cultured for the long term in a proliferative and undifferentiated state (2, 3). Here, we have used HNSC.100 neural stem cells that have been generated by infection of human neural progenitor cells, derived from the diencephalic and telencephalic region of a 10 -10.5-week gestational age aborted human fetus, with a v-Myc-encoding retrovirus (4). Like primary neural stem cells, HNSC.100 neural stem cells require mitogens (EGF, bFGF) in the growth medium. Grafting experiments into adult rat brain revealed that the stem cells integrated in a nondisruptive manner into the surrounding tissue (5).The fact that neural stem cells retain their potential to differentiate into the major cell types of the central nervous system lets them be considered as a useful cellular model system for studying the underlying cellular differentiation process. This includes the identification of transcription factors required for differentiation into a particular neural cell type as well as the analysis of the epigenetic changes that occur during differentiation. Chromatin remodeling, including differentiation-dependent changes in the histone methylation pattern, is known to occur during development and induces cell type-specific gene transcription. Using undifferentiated and differentiated human neural stem cells, we have investigated the regulation of a group of neuronal genes encoding synaptic vesicle proteins. 2 The abbreviations used are: EGF, epidermal growth factor; ERK, extracellular signal-regulated kinase; ER, estrogen receptor; GFAP, glial fibrillary acidic protein; NRSE, neural-restrictive silencer element; 4OHT, 4-hydroxytamoxifen; REST, RE-1 silencing transcription factor; TSA, trichostatin A; bFGF, basic fibroblast growth factor; RT, reverse transcriptase.

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Brain-derived neurotrophic factor-, epidermal growth factor-, or A-Raf-induced growth of HaCaT keratinocytes requires extracellular signal-regulated kinase

Cited by 25 publications

References 43 publications

Epidermal-growth-factor-induced proliferation of astrocytes requires Egr transcription factors

Epidermal-growth-factor-induced proliferation of astrocytes requires Egr transcription factors

Thapsigargin Induces Expression of Activating Transcription Factor 3 in Human Keratinocytes Involving Ca2+ Ions and c-Jun N-Terminal Protein Kinase

Transcription of Genes Encoding Synaptic Vesicle Proteins in Human Neural Stem Cells

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