Functional role of extracellular signal-regulated kinase activation and c-Jun induction in phorbol ester-induced promoter activation of human 12(S)-lipoxygenase gene

2002 ◽  
Vol 9 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Ben-Kuen Chen ◽  
Tein-Yi Tsai ◽  
Huei-Sheng Huang ◽  
Lei-Chin Chen ◽  
Wei-Chiao Chang ◽  
...  
Keyword(s):  
Phorbol Ester ◽  
Functional Role ◽  
Promoter Activation ◽  
Kinase Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Lipoxygenase Gene

Load-induced focal adhesion kinase activation in the myocardium: role of stretch and contractile activity

2002 ◽  
Vol 282 (2) ◽  
pp. H556-H564 ◽  
Author(s):  
Priscila P. Domingos ◽  
Priscila M. Fonseca ◽  
Wilson Nadruz ◽  
Kleber G. Franchini
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Diastolic Pressure ◽  
Contractile Activity ◽  
Kinase Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Signaling Complex ◽  
Extracellular Signal ◽  
Rat Hearts

We investigated the influence of stretch and contractile activity on load-induced activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK)1/2 in isolated rat hearts. Increases of diastolic pressure from ∼0 to ∼15 mmHg rapidly increased FAK tyrosine phosphorylation (maximum: 2.3-fold) and binding to c-Src (maximum: 2.8-fold) and Grb2 (maximum: 3.6-fold). This was paralleled by activation (maximum: 2.8-fold) and binding of ERK1/2 to FAK. FAK and ERK1/2 were immunolocalized at sarcolemmal sites of cardiac myocytes and in the nuclei, in the case of ERK1/2. Balloon inflation to raise ventricular pressure in hearts perfused with cardioplegic solution also activated FAK and ERK1/2. However, increases in contractile activity induced by increasing calcium concentration in the perfusate (from 0.5 to 5 mM) did not activate the FAK multicomponent signaling complex or ERK1/2 in the myocardium. These results indicate that stretch rather than contractile activity induces FAK and ERK1/2 activation in the myocardium. In addition, the activation and binding of ERK1/2 to FAK suggest that FAK drives the load-induced activation of ERK1/2.

β-Arrestin-recruited phosphodiesterase-4 desensitizes the AKAP79/PKA-mediated switching of β2-adrenoceptor signalling to activation of ERK

2005 ◽  
Vol 33 (6) ◽  
pp. 1333-1336 ◽  
Author(s):  
M.D. Houslay ◽  
G.S. Baillie
Keyword(s):  
Functional Role ◽  
Dominant Negative ◽  
Functional Importance ◽  
Extracellular Signal Regulated Kinase ◽  
Phosphodiesterase 4 ◽  
Camp Synthesis ◽  
Extracellular Signal ◽  
Anchoring Protein ◽  
Interfering Rna

Using combined dominant-negative and siRNA (small interfering RNA)-mediated knockdown strategies, the functional importance of specific PDE4 (phosphodiesterase-4) isoforms in modifying signalling through the β2-AR (β2-adrenoceptor) has been uncovered. The PDE4D5 isoform preferentially interacts with the signalling scaffold protein β-arrestin and is thereby recruited to the β2-AR upon agonist challenge. Delivery of an active PDE to the site of cAMP synthesis at the plasma membrane specifically attenuates the activity of a pool of PKA (protein kinase A) that is tethered to the β2-AR via AKAP79 (A-kinase anchoring protein 79). The specific functional role of this anchored PKA is to phosphorylate the β2-AR and allow it to switch its coupling with Gi and thereby activation of ERK (extracellular-signal-regulated kinase). Our studies uncover a novel facet of the regulation of β2-AR signalling by showing that β-arrestin-recruited PDE4 provides the means of desensitizing the agonist-dependent coupling of β2-AR with Gi and its consequential activation of ERK.

ERK5 and its role in tumour development

2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Invasion And Migration ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Tumour Cell Invasion ◽  
And Migration

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

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