|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
42
|
|
pubmed:dateCreated |
2003-10-13
|
|
pubmed:abstractText |
Glycogen synthase kinase-3beta (GSK-3beta) activity is suppressed when it becomes phosphorylated on serine 9 by protein kinase B (Akt). To determine how GSK-3beta activity opposes Akt function we used various methods to alleviate GSK-3beta suppression in prostate carcinoma cells. In some experiments, LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (a kinase involved in activating Akt) and tumor necrosis factor-alpha (TNF-alpha) were used to activate GSK-3beta. In other experiments mutant forms of GSK-3beta, GSK-3betadelta9 (a constitutively active deletion mutant of GSK-3beta) and GSK-3betaY216F (an inactive point mutant of GSK-3beta) were used to alter GSK-3beta activity. LY294002, TNF-alpha, and overexpression of wild-type GSK-3beta or of GSK-3betadelta9, but not GSK-3betaY216F, alleviated the suppression of GSK-3beta activity in prostate carcinoma cells and enhanced the turnover of beta-catenin. Forced expression of wild-type GSK-3beta or of GSK-3betadelta9, but not GSK-3betaY216F, suppressed cell growth and showed that the phosphorylation status of GSK-3beta can affect its intracellular distribution. When transcription factors activator protein-1 and cyclic AMP-response element (CRE)-binding protein were analyzed as targets of GSK-3beta activity, overexpression of wild-type GSK-3beta suppressed AP1-mediated transcription and activated CRE-mediated transcription. Overexpression of GSK-3betadelta9 caused an (80-fold) increase in CRE-mediated transcription, which was further amplified (up to 130-fold) by combining GSK-3betadelta9 overexpression with the suppression of Jun activity. This study also demonstrated for the first time that expression of constitutively active GSK-3betadelta9 results in the phosphorylation of CRE-binding protein on serine 129 and enhancement of CRE-mediated transcription in intact cell nuclei.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
17
|
|
pubmed:volume |
278
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
41338-46
|
|
pubmed:dateRevised |
2011-11-2
|
|
pubmed:meshHeading |
pubmed-meshheading:12900420-Blotting, Western,
pubmed-meshheading:12900420-Cell Division,
pubmed-meshheading:12900420-Cell Line, Tumor,
pubmed-meshheading:12900420-Cell Nucleus,
pubmed-meshheading:12900420-Chromones,
pubmed-meshheading:12900420-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:12900420-DNA, Complementary,
pubmed-meshheading:12900420-Densitometry,
pubmed-meshheading:12900420-Enzyme Inhibitors,
pubmed-meshheading:12900420-Glycogen Synthase Kinase 3,
pubmed-meshheading:12900420-Humans,
pubmed-meshheading:12900420-Luciferases,
pubmed-meshheading:12900420-Microscopy, Fluorescence,
pubmed-meshheading:12900420-Models, Molecular,
pubmed-meshheading:12900420-Morpholines,
pubmed-meshheading:12900420-Mutation,
pubmed-meshheading:12900420-Peptides,
pubmed-meshheading:12900420-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12900420-Phosphorylation,
pubmed-meshheading:12900420-Protein Structure, Tertiary,
pubmed-meshheading:12900420-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12900420-Proto-Oncogene Proteins,
pubmed-meshheading:12900420-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12900420-Serine,
pubmed-meshheading:12900420-Time Factors,
pubmed-meshheading:12900420-Transcription, Genetic,
pubmed-meshheading:12900420-Transcription Factor AP-1,
pubmed-meshheading:12900420-Transcriptional Activation,
pubmed-meshheading:12900420-Transfection,
pubmed-meshheading:12900420-Tumor Necrosis Factor-alpha
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Alleviating the suppression of glycogen synthase kinase-3beta by Akt leads to the phosphorylation of cAMP-response element-binding protein and its transactivation in intact cell nuclei.
|
|
pubmed:affiliation |
Departments of Clinical Cancer Prevention and Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
