Identification of new Nerve Growth Factor-responsive immediate-early genes

Dijkmans, Thomas F.; Hooijdonk, Lenneke W.A. van; Schouten, Theo G.; Kamphorst, Jessica T.; Fitzsimons, Carlos P.; Vreugdenhil, Erno

doi:10.1016/j.brainres.2008.10.050

Cited by 50 publications

(59 citation statements)

References 67 publications

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“…Since ERK5 has been a focus of interests in cardiovascular diseases, we searched the literature in the vascular system and found that KLF4 has been reported to be an important mediator for ERK5 (Ohnesorge et al 2010;Clark et al 2011;Sunadome et al 2011). Importantly, NGF has been reported to transiently up-regulate KLF4 mRNA level in PC12 cells (Dijkmans et al 2009). These data support the likelihood that KLF4 is a plausible target of the neuroprotective/ERK5 pathway.…”

Section: Ngf and Pc Up-regulated The Expression Of Klf4mentioning

confidence: 99%

“…To test the hypothesis that KLF4 is a downstream target of NGF and PC in PC12 cells, we measured KLF4 mRNA and protein levels in response to NGF or PC stimulation. Given that KLF4 has generally been considered as an early response gene in various tissues (Dijkmans et al 2009;Godmann et al 2010), coupled with our observation that its potential upstream activator, ERK5, was activated by NGF or PC within an hour of stimulation (Fig. 2), we used the time frame of 1 to 6 h to assess the effect of NGF and PC on KLF4 expression.…”

Section: Ngf and Pc Up-regulated The Expression Of Klf4mentioning

confidence: 99%

“…During a recent large-scale screening, Dijkmans et al identified KLF4 as a major immediate-early gene induced by NGF in the rat pheochromocytoma PC12 cells (Dijkmans et al 2009). PC12 cells have been widely used as a model to elucidate the mechanisms by which NGF exerts its anti-apoptotic effects (Greene 1978).…”

Section: Introductionmentioning

confidence: 99%

“…PC12 cells have been widely used as a model to elucidate the mechanisms by which NGF exerts its anti-apoptotic effects (Greene 1978). In Dijkmans' report, the authors found that the NGFinduced increase in KLF4 expression was partially abolished by U0126 (inhibitor against MEK1/2 and MEK5), suggesting an involvement of the ERKs (Dijkmans et al 2009). Given that ERK5 signaling induces KLF4 expression in peripheral cells to counteract apoptosis (Ohnesorge et al 2010), and that NGF activates ERK5 in PC12 cells (Obara et al 2009), we hypothesized that NGF and/or PC protects neuronal cells from apoptosis via activation of an ERK5/KLF4 pathway.…”

Section: Introductionmentioning

confidence: 99%

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ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning

Sun

Cunningham

et al. 2014

AGE

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Oxidative stress has long been implicated in the pathogenesis of various neurodegenerative disorders such as Alzheimer's disease and stroke. While high levels of oxidative stress are generally associated with cell death, a slight rise of reactive oxygen species (ROS) levels can be protective by "preconditioning" cells to develop a resistance against subsequent challenges. However, the mechanisms underlying such preconditioning (PC)-induced protection are still poorly understood. Previous studies have supported a role of ERK5 (mitogen-activated protein [MAP] kinase 5) in neuroprotection and ischemic tolerance in the hippocampus. In agreement with these findings, our data suggest that ERK5 mediates both hydrogen peroxide (H 2 O 2 )-induced PC as well as nerve growth factor (NGF)-induced neuroprotection. Activation of ERK5 partially rescued pheochromocytoma PC12 cells as well as primary hippocampal neurons from H 2 O 2 -caused death, while inhibition of ERK5 abolished NGF or PC-induced protection. These results implicate ERK5 signaling as a common downstream pathway for NGF and PC.Furthermore, both NGF and PC increased the expression of the transcription factor, KLF4, which can initiate an anti-apoptotic response in various cell types. Induction of KLF4 by NGF or PC was blocked by siERK5, suggesting that ERK5 is required in this process. siKLF4 can also attenuate NGF-or PC-induced neuroprotection. Overexpression of active MEK5 or KLF4 in H 2 O 2 -stressed cells increased Bcl-2/Bax ratio and the expression of NAIP (neuronal apoptosis inhibitory protein). Taken together, our data suggest that ERK5/KLF4 cascade is a common signaling pathway shared by at least two important mechanisms by which neurons can be protected from cell death.

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Section: Ngf and Pc Up-regulated The Expression Of Klf4mentioning

confidence: 99%

Section: Ngf and Pc Up-regulated The Expression Of Klf4mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning

Sun

Cunningham

et al. 2014

AGE

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“…The first wave of the EGFR-induced transcriptional response (IEGs; immediate early genes) contains predominantly transcriptional activators; the second, delayed response wave (DEGs), involves multiple inhibitors of gene transcription that act at different levels (Amit et al 2007). For instance, the proteins MafF and Kruppel-like factor 2 (KLF2) induced by RTKs (Amit et al 2007;Dijkmans et al 2009;Dutta et al 2011) are negative regulators of several promoter elements, including the serum response element (SRE) (Amit et al 2007). SRE is found within promoters of multiple IEG, such as transcription factors c-fos and egr-1, and a negative signaling regulator DUSP6 (Christy and Nathans 1989;Rivera et al 1990;Treisman 1995;Bluthgen et al 2009).…”

Section: Feedback Loops Operating Within Transcriptional Circuitsmentioning

confidence: 99%

Complexity of Receptor Tyrosine Kinase Signal Processing

Volinsky

Kholodenko

2013

Cold Spring Harbor Perspectives in Biology

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Our knowledge of molecular mechanisms of receptor tyrosine kinase (RTK) signaling advances with ever-increasing pace. Yet our understanding of how the spatiotemporal dynamics of RTK signaling control specific cellular outcomes has lagged behind. Systems-centered experimental and computational approaches can help reveal how overlapping networks of signal transducers downstream of RTKs orchestrate specific cell-fate decisions. We discuss how RTK network regulatory structures, which involve the immediate posttranslational and delayed transcriptional controls by multiple feed forward and feedback loops together with pathway cross talk, adapt cells to the combinatorial variety of external cues and conditions. This intricate network circuitry endows cells with emerging capabilities for RTK signal processing and decoding. We illustrate how mathematical modeling facilitates our understanding of RTK network behaviors by unraveling specific systems properties, including bistability, oscillations, excitable responses, and generation of intricate landscapes of signaling activities.

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Functional role of KLF10 in multiple disease processes

et al. 2010

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Since the discovery by this laboratory of the zinc finger transcription factor, KLF10, a member of the Krüppel-like family of transcription factors, there have been multiple publications regarding its functions and its immediate family members, in numerous cell types. KLF10 has been shown to be rapidly induced by TGFβ1, 2, 3, E2, epidermal growth factor, and bone morphogenetic protein-2. TGFβ inducible early gene-1 activates the TGFβ-Smad signaling pathway via repression of Smad 7 expression and activation of Smad 2 expression and activity. Overall, KLF10 has been implicated in cell differentiation, as a target gene for a variety of signaling pathways, and in serving as a potential marker for human diseases such as breast cancer, cardiac hypertrophy, and osteoporosis. Like other KLF members, KLF10 is expressed in specific cell types in numerous tissues and is known to be involved in repressing cell proliferation and inflammation as well as inducing apoptosis similar to that of TGFβ KLF10 binds to Sp-1-GC rich DNA sequences and can activate or repress the transcription of a number of genes. Overall, KLF10 has been shown to play a major role in the TGFβ inhibition of cell proliferation and inflammation and induction of apoptosis, and its overexpression in human osteoblasts and pancreatic carcinoma cells mimics the actions of TGFβ.

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Identification of new Nerve Growth Factor-responsive immediate-early genes

Cited by 50 publications

References 67 publications

ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning

ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning

Complexity of Receptor Tyrosine Kinase Signal Processing

Functional role of KLF10 in multiple disease processes

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