Linked Life Data

17721885

Source:http://linkedlifedata.com/resource/pubmed/id/17721885

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-4-2
pubmed:abstractText
Insulin receptor substrate (IRS) proteins are important docking proteins in mediating the insulin signaling cascade. We have investigated the effect of short interfering RNA (siRNA) mediated knockdown of IRS-1 on insulin signaling cascade in primary human hepatocellular carcinoma HepG2 cell line and HepG2 cells overexpressing Akt1/PKB-alpha (HepG2-CA-Akt/PKB). IRS-1 knockdown in both cell lines resulted in reduction of insulin stimulated Akt1 phosphorylation at Ser 473. In parental HepG2 cells, IRS-1 knockdown resulted in reduction (ca. 50%) in the basal level of phosphorylated mTOR (Ser 2448) irrespective of insulin treatment. In contrast, HepG2-CA-Akt/PKB cells showed an upregulation in the basal level of phosphorylated mTOR (Ser 2448) (ca. 40%). Insulin mediated phosphorylation of mTOR was reduced. IRS-1 knockdown also reduced the cell proliferation of parental HepG2 cells by ca. 30% in the presence/absence of insulin, whereas in HepG2-CA-Akt/PKB the cell proliferation was reduced by 15% and treatment of insulin further reduced it to ca. 50% (vs. control). IRS-1 knockdown also reduced the glycogen synthase (GS) activity in parental HepG2 cells, however, it was upregulated in HepG2-CA-Akt/PKB cells. These results suggest that knockdown of IRS-1 abolished basal as well as insulin mediated phosphorylation/activity of proteins involved in cell proliferation or glycogen metabolism in the parental Hep2 cells. IRS-1 knockdown in cells overexpressing constitutively active Akt1/PKB-alpha either did not change or upregulated the basal levels of phosphorylated/active proteins. However, insulin mediated response was either not altered or downregulated in these cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Glycogen, http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase, http://linkedlifedata.com/resource/pubmed/chemical/IRS1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Insulin Receptor Substrate Proteins, http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1097-4644
pubmed:author
pubmed:copyrightInfo
2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1424-37
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Overexpression of Akt1 upregulates glycogen synthase activity and phosphorylation of mTOR in IRS-1 knockdown HepG2 cells.
pubmed:affiliation
Department of Biochemistry, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Canada S7N 5E5.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't