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rdf:type |
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lifeskim:mentions |
umls-concept:C0007608,
umls-concept:C0018270,
umls-concept:C0227525,
umls-concept:C0333117,
umls-concept:C0439590,
umls-concept:C0521447,
umls-concept:C0600388,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1879547
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pubmed:issue |
31
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pubmed:dateCreated |
2002-7-29
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pubmed:abstractText |
We examined the signaling pathway by which hepatocyte growth factor (HGF) induces cell motility, with special focus on the role of extracellular signal-regulated kinase (ERK) in the nucleus. We used Madin-Darby canine kidney cells overexpressing ERK2 because of their prominent motility response to HGF. HGF stimulation of the cells induces not only a rapid, marked, and sustained activation and rapid nuclear accumulation of ERK1/2, but also a prolonged nuclear retention of the activated ERK1/2. Interruption of the ERK1/2 activation by PD98059 treatment of the cells 30 min after HGF stimulation abolishes the HGF-induced cell motility. Enforced cytoplasmic retention of the activated ERK1/2 by the expression of an inactive form of MKP-3 cytoplasmic phosphatase inhibits the cell motility response. Although epidermal growth factor stimulation of the cells induces the activation and nuclear accumulation of ERK1/2, it does not induce the prolonged nuclear retention of the activated ERK1/2, and fails to induce cell motility. In the nucleus, activated ERK1/2 continuously phosphorylate Elk-1, leading to the prolonged expression of c-fos, which results in the expression of several genes such as matrix metalloproteinase (mmp)-9; MMP-9 activity is required for the induction of the cell motility response. Our results indicate that the sustained activity of ERK1/2 in the nucleus is required for the induction of HGF-induced cell motility.
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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/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Map2k1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28256-64
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12032150-Active Transport, Cell Nucleus,
pubmed-meshheading:12032150-Animals,
pubmed-meshheading:12032150-Cell Line,
pubmed-meshheading:12032150-Cell Movement,
pubmed-meshheading:12032150-Cell Nucleus,
pubmed-meshheading:12032150-Dogs,
pubmed-meshheading:12032150-Enzyme Activation,
pubmed-meshheading:12032150-Epidermal Growth Factor,
pubmed-meshheading:12032150-Hepatocyte Growth Factor,
pubmed-meshheading:12032150-Hepatocytes,
pubmed-meshheading:12032150-Kidney,
pubmed-meshheading:12032150-MAP Kinase Kinase 1,
pubmed-meshheading:12032150-Mice,
pubmed-meshheading:12032150-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:12032150-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:12032150-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:12032150-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12032150-Phosphorylation,
pubmed-meshheading:12032150-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12032150-Recombinant Fusion Proteins,
pubmed-meshheading:12032150-Recombinant Proteins,
pubmed-meshheading:12032150-Transfection
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pubmed:year |
2002
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pubmed:articleTitle |
Prolonged nuclear retention of activated extracellular signal-regulated kinase 1/2 is required for hepatocyte growth factor-induced cell motility.
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pubmed:affiliation |
Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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