Immediate-early gene activation by the MAPK pathways: what do and don't we know?

2012 ◽  
Vol 40 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Amanda O'Donnell ◽  
Zaneta Odrowaz ◽  
Andrew D. Sharrocks
Keyword(s):  
Current Knowledge ◽  
Gene Activation ◽  
Immediate Early Gene ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Immediate Early ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Activation Mechanisms ◽  
Extracellular Signalling

The study of IE (immediate-early) gene activation mechanisms has provided numerous paradigms for how transcription is controlled in response to extracellular signalling. Many of the findings have been derived from investigating one of the IE genes, FOS, and the models extrapolated to regulatory mechanisms for other IE genes. However, whereas the overall principles of activation appear similar, recent evidence suggests that the underlying mechanistic details may differ depending on cell type, cellular stimulus and IE gene under investigation. In the present paper, we review recent advances in our understanding of IE gene transcription, chiefly focusing on FOS and its activation by ERK (extracellular-signal-regulated kinase) MAPK (mitogen-activated protein kinase) pathway signalling. We highlight important fundamental regulatory principles, but also illustrate the gaps in our current knowledge and the potential danger in making assumptions based on extrapolation from disparate studies.

scholarly journals A Network of Immediate Early Gene Products Propagates Subtle Differences in Mitogen-Activated Protein Kinase Signal Amplitude and Duration

2004 ◽  
Vol 24 (1) ◽  
pp. 144-153 ◽  
Author(s):  
Leon O. Murphy ◽  
Jeffrey P. MacKeigan ◽  
John Blenis
Keyword(s):  
Protein Kinase ◽  
Cell Fate ◽  
Signal Amplitude ◽  
Immediate Early Gene ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Immediate Early ◽  
General Mechanism ◽  
Mitogen Activated Protein

ABSTRACT The strength and duration of mitogen-activated protein kinase (MAPK) signaling have been shown to regulate cell fate in different cell types. In this study, a general mechanism is described that explains how subtle differences in signaling kinetics are translated into a specific biological outcome. In fibroblasts, the expression of immediate early gene (IEG)-encoded Fos, Jun, Myc, and early growth response gene 1 (Egr-1) transcription factors is significantly extended by sustained extracellular signal-regulated kinase 1 and 2 (ERK1 and -2) signaling. Several of these proteins contain functional docking site for ERK, FXFP (DEF) domains that serve to locally concentrate the active kinase, thus showing that they can function as ERK sensors. Sustained ERK signaling regulates the posttranslational modifications of these IEG-encoded sensors, which contributes to their sustained expression during the G1-S transition. DEF domain-containing sensors can also interpret the small changes in ERK signal strength that arise from less than a threefold reduction in agonist concentration. As a result, downstream target gene expression and cell cycle progression are significantly changed.

scholarly journals Role of oxidative stress in intermittent hypoxia-induced immediate early gene activation in rat PC12 cells

2004 ◽  
Vol 557 (3) ◽  
pp. 773-783 ◽  
Author(s):  
Guoxiang Yuan ◽  
Gautam Adhikary ◽  
Andrew A. McCormick ◽  
John. J. Holcroft ◽  
Ganesh K. Kumar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Intermittent Hypoxia ◽  
Gene Activation ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early

Increased immediate early gene activation in the basolateral amygdala following persistent peripheral inflammation.

Neuroreport ◽  
2020 ◽  
Vol 31 (10) ◽  
pp. 724-729
Author(s):  
Julio Cesar Morales-Medina ◽  
Ashutosh Rastogi ◽  
Eric Mintz ◽  
Heather K. Caldwell
Keyword(s):  
Basolateral Amygdala ◽  
Gene Activation ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Peripheral Inflammation

scholarly journals Sex and estrous cycle differences in immediate early gene activation in the hippocampus and the dorsal striatum after the cue competition task

2017 ◽  
Vol 87 ◽  
pp. 69-79 ◽  
Author(s):  
Shunya Yagi ◽  
Dimka Drewczynski ◽  
Steven R. Wainwright ◽  
Cindy K. Barha ◽  
Olivia Hershorn ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Gene Activation ◽  
Dorsal Striatum ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Cue Competition

scholarly journals Mip1, an MEKK2-Interacting Protein, Controls MEKK2 Dimerization and Activation

2005 ◽  
Vol 25 (14) ◽  
pp. 5955-5964 ◽  
Author(s):  
Jinke Cheng ◽  
Dongyu Zhang ◽  
Kihwan Kim ◽  
Yingxin Zhao ◽  
Yingming Zhao ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Wide Spectrum ◽  
Gene Activation ◽  
Mitogen Activated Protein Kinase ◽  
Interacting Protein ◽  
Mapk Kinase ◽  
Mapk Cascades ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Molecular Aspects

ABSTRACT Mitogen-activated protein kinase (MAPK) cascades are central components of the intracellular signaling networks used by eukaryotic cells to respond to a wide spectrum of extracellular stimuli. An MAPK is activated by an MAPK kinase, which in turn is activated by an MAPK kinase kinase (MAP3K). However, little is known about the molecular aspects of the regulation and activation of large numbers of MAP3Ks that are crucial in relaying upstream receptor-mediated signals through the MAPK cascades to induce various physiological responses. In this study, we identified a novel MEKK2-interacting protein, Mip1, that regulates MEKK2 dimerization and activation by forming a complex with inactive and nonphosphorylated MEKK2. In particular, Mip1 prevented MEKK2 activation by blocking MEKK2 dimer formation, which in turn blocked JNKK2, c-Jun N-terminal kinase 1 (JNK1), extracellular signal-regulated kinase 5, and AP-1 reporter gene activation by MEKK2. Furthermore, we found that the endogenous Mip1-MEKK2 complex was dissociated transiently following epidermal growth factor stimulation. In contrast, the knockdown of Mip1 expression by siRNA augmented the MEKK2-mediated JNK and AP-1 reporter activation. Together, our data suggest a novel model for MEKK2 regulation and activation.

scholarly journals Raf and Fibroblast Growth Factor Phosphorylate Elk1 and Activate the Serum Response Element of the Immediate Early Genepip92 by Mitogen-Activated Protein Kinase-Independent as Well as -Dependent Signaling Pathways

1998 ◽  
Vol 18 (4) ◽  
pp. 2272-2281 ◽  
Author(s):  
Kwang-Chul Chung ◽  
Ignatius Gomes ◽  
Danhui Wang ◽  
Lester F. Lau ◽  
Marsha Rich Rosner
Keyword(s):  
Growth Factor ◽  
Fusion Protein ◽  
Signaling Pathways ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Serum Response Element ◽  
Response Element ◽  
Mitogen Activated Protein ◽  
Serum Response

ABSTRACT Previous studies have shown that a mitogen activated protein (MAP) kinase (MEK)-independent signaling pathway is required by activated Raf or fibroblast-derived growth factor (FGF) for the differentiation of rat hippocampal neuronal H19-7 cells. We now demonstrate that both Raf and FGF similarly induce prolonged transcription and translation of the immediate early gene pip92 in the absence of activation of the MAP kinases (MAPKs) ERK1 and ERK2. To determine the mechanism by which this occurs and to identify novel Raf-activated signaling pathways, we investigated the induction of the pip92promoter by both FGF and an estradiol-activated Raf-1–estrogen receptor fusion protein (ΔRaf-1:ER) in H19-7 cells. Deletion analysis of the pip92 promoter indicated that activation by the MAPK-independent pathway occurs primarily within the region containing a serum response element (SRE). Further analysis of the SRE by using a heterologous thymidine kinase promoter showed that both an Ets and CArG-like site are required. Elk1, which binds to the Ets site, was phosphorylated both in vitro and in vivo by the MAPK-independent pathway, and phosphorylation of an Elk1-GAL4 fusion protein by this pathway was sufficient for transactivation. Finally, at least two Elk1 kinases were fractionated by gel filtration, and analysis by an in-gel kinase assay revealed at least three novel Raf-activated Elk1 kinases. These results indicate that both FGF and Raf activate MAPK-independent kinases that can stimulate Elk1 phosphorylation and immediate early gene transcription.

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