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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2010-12-17
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pubmed:abstractText |
It was previously shown that integrin ?6?4 contributes to translation of cancer-related mRNAs such as VEGF via initiation factor eIF4E. In this study, we found that integrin ?6?4 regulates the activity of eIF4E through the Ser/Thr kinase Mnk. Although a role for Mnk in various aspects of cancer progression has been established, a link between integrin and Mnk activity has not. Here we show that Mnk1 is a downstream effector of integrin ?6?4 and mediates the ?6?4 signaling, important for translational control. Integrin ?6?4 signals through MEK and p38 MAPK to increase phosphorylation of Mnk1 and eIF4E. Inhibition of Mnk1 activity by CGP57380 or downregulation by shRNA blocks ?6?4-dependent translation of VEGF mRNA. Our studies suggest that Mnk1 could be a therapeutic target in cancers where the integrin ?6?4 level is high.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Aniline Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Butadienes,
http://linkedlifedata.com/resource/pubmed/chemical/CGP 57380,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Eukaryotic Initiation Factor-4E,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha6beta4,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/MKNK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MKNK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Purines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/U 0126,
http://linkedlifedata.com/resource/pubmed/chemical/VEGFA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1557-3125
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pubmed:author |
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pubmed:copyrightInfo |
©2010 AACR.
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pubmed:issnType |
Electronic
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1571-8
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pubmed:meshHeading |
pubmed-meshheading:21047768-Aniline Compounds,
pubmed-meshheading:21047768-Butadienes,
pubmed-meshheading:21047768-Cell Growth Processes,
pubmed-meshheading:21047768-Cell Line, Tumor,
pubmed-meshheading:21047768-Culture Media, Serum-Free,
pubmed-meshheading:21047768-Down-Regulation,
pubmed-meshheading:21047768-Eukaryotic Initiation Factor-4E,
pubmed-meshheading:21047768-Humans,
pubmed-meshheading:21047768-Integrin alpha6beta4,
pubmed-meshheading:21047768-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:21047768-MAP Kinase Kinase Kinases,
pubmed-meshheading:21047768-Nitriles,
pubmed-meshheading:21047768-Phosphorylation,
pubmed-meshheading:21047768-Protein Biosynthesis,
pubmed-meshheading:21047768-Protein-Serine-Threonine Kinases,
pubmed-meshheading:21047768-Purines,
pubmed-meshheading:21047768-RNA, Messenger,
pubmed-meshheading:21047768-RNA, Small Interfering,
pubmed-meshheading:21047768-Vascular Endothelial Growth Factor A,
pubmed-meshheading:21047768-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2010
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pubmed:articleTitle |
Mnk mediates integrin ?6?4-dependent eIF4E phosphorylation and translation of VEGF mRNA.
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pubmed:affiliation |
Department of Emergency Medicine, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA. nkorne@lsuhsc.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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