Interleukin (IL)-4 and IL-13 up-regulate monocyte chemoattractant protein-1 expression in human bronchial epithelial cells: involvement of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2 and Janus kinase-2 but not c-Jun NH2-terminal kinase 1/2 signalling pathways

IL-6 (interleukin 6)-type cytokines are pleiotropic molecules, critical for cellular homoeostasis and with well-recognized roles in several human diseases. They all activate JAK (Janus kinase)/STAT (signal transducer and activator of transcription) signalling and, depending on the particular cytokine, cell type and cellular environment, they can also trigger the activation of MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinase) cascades. Although it is clear that JAK/STAT and MAPK reciprocally regulate each other, how these signalling pathways are fully integrated remains to be fully understood. Not only do cells have to be able to integrate and conciliate what are often contradictory signalling cues, but they are also subject to complex regulatory mechanisms involving these pathways. More specifically, we have shown recently that ERK2 (extracellular-signal-regulated kinase 2) is required for the transcriptional regulation of gp130 (glycoprotein 130), a key receptor complex component for most IL-6-type cytokines. ERK2 not only binds to the gp130 promoter and is required for full expression of the protein, but it also regulates the stability of gp130 mRNA. This function of ERK2 is not shared by ERK1 and it probably represents an entirely novel function for this prominent kinase.

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Faculty Opinions recommendation of Sequential activation of the MEK-extracellular signal-regulated kinase and MKK3/6-p38 mitogen-activated protein kinase pathways mediates oncogenic ras-induced premature senescence.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1006218.77810 ◽

2002 ◽

Author(s):

Angel Nebreda

Keyword(s):

Protein Kinase ◽

Mitogen Activated Protein Kinase ◽

Premature Senescence ◽

Extracellular Signal Regulated Kinase ◽

Oncogenic Ras ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

Sequential Activation

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ERK5 and its role in tumour development

Biochemical Society Transactions ◽

10.1042/bst20110663 ◽

2012 ◽

Vol 40 (1) ◽

pp. 251-256 ◽

Cited By ~ 50

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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