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rdf:type |
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lifeskim:mentions |
umls-concept:C0033414,
umls-concept:C0109317,
umls-concept:C0752312,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366876,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1518440,
umls-concept:C1705767,
umls-concept:C1705791
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pubmed:issue |
3
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pubmed:dateCreated |
2007-2-8
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pubmed:abstractText |
Spatial regulation of ERK1/2 MAP kinases is an essential yet largely unveiled mechanism for ensuring the fidelity and specificity of their signals. Mxi2 is a p38alpha isoform with the ability to bind ERK1/2. Herein we show that Mxi2 has profound effects on ERK1/2 nucleocytoplasmic distribution, promoting their accumulation in the nucleus. Downregulation of endogenous Mxi2 by RNAi causes a marked reduction of ERK1/2 in the nucleus, accompanied by a pronounced decline in cellular proliferation. We demonstrate that Mxi2 functions in nuclear shuttling of ERK1/2 by enhancing the nuclear accumulation of both phosphorylated and unphosphorylated forms in the absence of stimulation. This process requires the direct interaction of both proteins and a high-affinity binding of Mxi2 to ERK-binding sites in nucleoporins, In this respect, Mxi2 acts antagonistically to PEA15, displacing it from ERK1/2 complexes. These results point to Mxi2 as a key spatial regulator for ERK1/2 and disclose an unprecedented stimulus-independent mechanism for ERK nuclear import.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-10508167,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-10601328,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-10704436,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-10838079,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-11134045,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-11294822,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-11328824,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-11546808,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-11702783,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-11739740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-12032311,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-12697810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-12899687,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-14707138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-15068802,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-15173174,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-15546878,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-16324895,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-16595679,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-3805121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-7479834,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-7568036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-8394845,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-9155016,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-9384386,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-9604935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-9744882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-9768359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-9799732,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17255949-9925641
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
635-46
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17255949-Active Transport, Cell Nucleus,
pubmed-meshheading:17255949-Animals,
pubmed-meshheading:17255949-Cell Line,
pubmed-meshheading:17255949-Cell Nucleus,
pubmed-meshheading:17255949-Cercopithecus aethiops,
pubmed-meshheading:17255949-Dogs,
pubmed-meshheading:17255949-Fluorescent Antibody Technique,
pubmed-meshheading:17255949-Humans,
pubmed-meshheading:17255949-Immunoblotting,
pubmed-meshheading:17255949-Immunoprecipitation,
pubmed-meshheading:17255949-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17255949-Mitogen-Activated Protein Kinase 14,
pubmed-meshheading:17255949-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:17255949-Models, Biological,
pubmed-meshheading:17255949-Nuclear Pore Complex Proteins,
pubmed-meshheading:17255949-Phosphoproteins,
pubmed-meshheading:17255949-RNA Interference
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pubmed:year |
2007
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pubmed:articleTitle |
Mxi2 promotes stimulus-independent ERK nuclear translocation.
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pubmed:affiliation |
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas (CSIC), Departamento de Biología Molecular, Unidad de Biomedicina CSIC--Universidad de Cantabria, Santander, Spain.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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