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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2008-5-29
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pubmed:abstractText |
Isoform A of phosphatidylinositol 3-kinase enhancer (PIKE-A) is a newly identified prooncogenic factor that has been implicated in cancer cell growth. How PIKE-A activity is regulated in response to growth signal is poorly understood. Here, we demonstrate that cyclin dependent kinase 5 (Cdk5), a protein known to function mainly in postmitotic neurons, directly phosphorylates PIKE-A at Ser-279 in its GTPase domain in glioblastoma cells. This phosphorylation event stimulates PIKE-A GTPase activity and the activity of its downstream effector Akt. Growth signal activates Cdk5 and results in a Cdk5-dependent accumulation of phosphorylated PIKE-A and activation of Akt in the nucleus. Furthermore, PIKE-A phosphorylation and Cdk5 are increased in human glioblastoma specimens. Phosphorylation of PIKE-A by Cdk5 mediates growth factor-induced migration and invasion of human glioblastoma cells. Together, these findings identify PIKE as the first Cdk5 target in cancer cells, revealing a previously undescribed regulatory mechanism that mediates growth signal-induced activation of PIKE-A/Akt and tumor invasion.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-11136977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-11160434,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-11228158,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-11296485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-11909854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-12640130,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-12691662,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-13130092,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-14676271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-14748662,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-14761976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-15118108,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-15135890,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-15194121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-15385964,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-15520182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-15800333,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-15888658,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-16263930,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-16407541,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-16885348,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-16998837,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-17081516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-17145757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-17297440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-17320297,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-18042622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-8724849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18487454-9407321
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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 |
May
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
27
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7570-5
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pubmed:dateRevised |
2011-10-14
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pubmed:meshHeading |
pubmed-meshheading:18487454-Active Transport, Cell Nucleus,
pubmed-meshheading:18487454-Cell Line, Tumor,
pubmed-meshheading:18487454-Cell Movement,
pubmed-meshheading:18487454-Central Nervous System Neoplasms,
pubmed-meshheading:18487454-Cyclin-Dependent Kinase 5,
pubmed-meshheading:18487454-GTP-Binding Proteins,
pubmed-meshheading:18487454-GTPase-Activating Proteins,
pubmed-meshheading:18487454-Glioblastoma,
pubmed-meshheading:18487454-Humans,
pubmed-meshheading:18487454-Neoplasm Invasiveness,
pubmed-meshheading:18487454-Phosphorylation,
pubmed-meshheading:18487454-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18487454-Serine
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pubmed:year |
2008
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pubmed:articleTitle |
Cdk5-mediated regulation of the PIKE-A-Akt pathway and glioblastoma cell invasion.
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pubmed:affiliation |
Departments of Pharmacology, Neurology, and Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
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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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