Linked Life Data

18814837

Source:http://linkedlifedata.com/resource/pubmed/id/18814837

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-10-30
pubmed:abstractText
Differential activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway has been linked to cancer. Activation occurs through gene amplification and activating mutations. High-frequency mutations in the gene encoding the p110alpha catalytic subunit of PI3K (PIK3CA) have been observed in a variety of tumors including colon, brain, breast, ovarian, and gastric. Inhibition of PI3K kinase activity may provide a specific way to treat multiple types of human cancer. A scintillation proximity assay (SPA) was developed to detect phosphatidylinositol 3-kinase catalytic activity. Using this assay format, steady-state kinetic parameters were compared for the PI3K class IA enzymes p110alpha, p110beta, and p110delta, each coexpressed with the regulatory subunit p85alpha or splice variant p55alpha. Inhibition by the natural product wortmannin and LY294002 was detected with potencies consistent with alternate assay formats. Other biochemical assay formats have been described for phosphoinositide 3-kinases but each has its unique limitations. The simple, inexpensive, sensitive high-throughput nature of the SPA format has advanced our knowledge of isoform-specific enzymology and will facilitate the discovery of novel PI3K inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1096-0309
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
383
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
311-5
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Characterization of PI3K class IA isoforms with regulatory subunit p55alpha using a scintillation proximity assay.
pubmed:affiliation
Department of Enzymology and Mechanistic Pharmacology, Oncology CEDD, GlaxoSmithKline, Collegeville, PA 19426, USA. glenn.s.van.aller@gsk.com
pubmed:publicationType
Journal Article