Linked Life Data

21419339

Source:http://linkedlifedata.com/resource/pubmed/id/21419339

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-3-22
pubmed:abstractText
Phosphoinositide 3-kinase ? (PI3K?) is activated by G protein-coupled receptors (GPCRs). We show here that PI3K? inhibits protein phosphatase 2A (PP2A) at the ?-adrenergic receptor (?AR, a GPCR) complex altering G protein coupling. PI3K? inhibition results in significant increase of ?AR-associated phosphatase activity leading to receptor dephosphorylation and resensitization preserving cardiac function. Mechanistically, PI3K? inhibits PP2A activity at the ?AR complex by phosphorylating an intracellular inhibitor of PP2A (I2PP2A) on serine residues 9 and 93, resulting in enhanced binding to PP2A. Indeed, enhanced phosphorylation of ?2ARs is observed with a phosphomimetic I2PP2A mutant that was completely reversed with a mutant mimicking dephosphorylated state. siRNA depletion of endogenous I2PP2A augments PP2A activity despite active PI3K resulting in ?2AR dephosphorylation and sustained signaling. Our study provides the underpinnings of a PI3K?-mediated regulation of PP2A activity that has significant consequences on receptor function with broad implications in cellular signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1097-4164
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
636-48
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Inhibition of protein phosphatase 2A activity by PI3K? regulates ?-adrenergic receptor function.
pubmed:affiliation
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural