Modulation of human cytomegalovirus immediate-early gene enhancer by mitogen-activated protein kinase kinase kinase-1

2001 ◽  
Vol 83 (4) ◽  
pp. 563-573 ◽  
Author(s):  
Bin Sun ◽  
Greg Harrowe ◽  
Christoph Reinhard ◽  
Corinne Yoshihara ◽  
Keting Chu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Human Cytomegalovirus ◽  
Immediate Early Gene ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Immediate Early ◽  
Gene Enhancer ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

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 Protein synthesis inhibitors reveal differential regulation of mitogen-activated protein kinase and stress-activated protein kinase pathways that converge on Elk-1.

1995 ◽  
Vol 15 (9) ◽  
pp. 4930-4938 ◽  
Author(s):  
R Zinck ◽  
M A Cahill ◽  
M Kracht ◽  
C Sachsenmaier ◽  
R A Hipskind ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Early Gene ◽  
Immediate Early ◽  
Protein Synthesis Inhibitors ◽  
Mitogen Activated Protein

Inhibitors of protein synthesis, such as anisomycin and cycloheximide, lead to superinduction of immediate-early genes. We demonstrate that these two drugs activate intracellular signaling pathways involving both the mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK) cascades. The activation of either pathway correlates with phosphorylation of the c-fos regulatory transcription factor Elk-1. In HeLa cells, anisomycin stabilizes c-fos mRNA when protein synthesis is inhibited to only 50%. Under these conditions, anisomycin, in contrast to cycloheximide, rapidly induces kinase activation and efficient Elk-1 phosphorylation. However, full inhibition of translation by either drug leads to prolonged activation of SAPK activity, while MAPK induction is transient. This correlates with prolonged Elk-1 phosphorylation and c-fos transcription. Elk-1 induction and c-fos activation are also observed in KB cells, in which anisomycin strongly induces SAPKs but not MAPKs. Purified p54 SAPK alpha efficiently phosphorylates the Elk-1 C-terminal domain in vitro and comigrates with anisomycin-activated kinases in in-gel kinase assays. Thus, Elk-1 provides a potential convergence point for the MAPK and SAPK signaling pathways. The activation of signal cascades and control of transcription factor function therefore represent prominent processes in immediate-early gene superinduction.

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.

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