|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2011-4-8
|
|
pubmed:abstractText |
Adrenergic stimulation of the heart engages cAMP and phosphoinositide second messenger signaling cascades. Cardiac phosphoinositide 3-kinase p110? participates in these processes by sustaining ?-adrenergic receptor internalization through its catalytic function and by controlling phosphodiesterase 3B (PDE3B) activity via an unknown kinase-independent mechanism. We have discovered that p110? anchors protein kinase A (PKA) through a site in its N-terminal region. Anchored PKA activates PDE3B to enhance cAMP degradation and phosphorylates p110? to inhibit PIP(3) production. This provides local feedback control of PIP(3) and cAMP signaling events. In congestive heart failure, p110? is upregulated and escapes PKA-mediated inhibition, contributing to a reduction in ?-adrenergic receptor density. Pharmacological inhibition of p110? normalizes ?-adrenergic receptor density and improves contractility in failing hearts.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-quinoxalin-6-ylmethylenethiazolidi...,
http://linkedlifedata.com/resource/pubmed/chemical/A Kinase Anchor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Class Ib Phosphatidylinositol...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/PDE3B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PIK3CG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PRKAR2A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Pik3cg protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/phosphatidylinositol...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Apr
|
|
pubmed:issn |
1097-4164
|
|
pubmed:author |
pubmed-author:AltrudaFiorellaF,
pubmed-author:BaillieGeorge SGS,
pubmed-author:DamilanoFedericoF,
pubmed-author:DunlopAllan JAJ,
pubmed-author:FerreroEnricoE,
pubmed-author:GhigoAlessandraA,
pubmed-author:HeymansStephaneS,
pubmed-author:HirschEmilioE,
pubmed-author:HouslayMiles DMD,
pubmed-author:IaccarinoGuidoG,
pubmed-author:LangebergLorene KLK,
pubmed-author:LemboGiuseppeG,
pubmed-author:LeviRenzoR,
pubmed-author:MorelloFulvioF,
pubmed-author:NeubauerGitteG,
pubmed-author:PawsonCatherineC,
pubmed-author:PerinoAlessiaA,
pubmed-author:SantulliGaetanoG,
pubmed-author:ScottJohn DJD,
pubmed-author:SilengoLorenzoL,
pubmed-author:WalserRomyR,
pubmed-author:WetzkerReinhardR,
pubmed-author:WymannMatthias PMP
|
|
pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
8
|
|
pubmed:volume |
42
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
84-95
|
|
pubmed:meshHeading |
pubmed-meshheading:21474070-A Kinase Anchor Proteins,
pubmed-meshheading:21474070-Amino Acid Sequence,
pubmed-meshheading:21474070-Animals,
pubmed-meshheading:21474070-Base Sequence,
pubmed-meshheading:21474070-Cell Line,
pubmed-meshheading:21474070-Class Ib Phosphatidylinositol 3-Kinase,
pubmed-meshheading:21474070-Cyclic AMP,
pubmed-meshheading:21474070-Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit,
pubmed-meshheading:21474070-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:21474070-Cyclic Nucleotide Phosphodiesterases, Type 3,
pubmed-meshheading:21474070-DNA,
pubmed-meshheading:21474070-Enzyme Activation,
pubmed-meshheading:21474070-Enzyme Inhibitors,
pubmed-meshheading:21474070-Heart Failure,
pubmed-meshheading:21474070-Humans,
pubmed-meshheading:21474070-Mice,
pubmed-meshheading:21474070-Mice, Inbred C57BL,
pubmed-meshheading:21474070-Mice, Knockout,
pubmed-meshheading:21474070-Molecular Sequence Data,
pubmed-meshheading:21474070-Myocytes, Cardiac,
pubmed-meshheading:21474070-Peptide Fragments,
pubmed-meshheading:21474070-Phosphatidylinositol Phosphates,
pubmed-meshheading:21474070-Phosphorylation,
pubmed-meshheading:21474070-Protein Interaction Mapping,
pubmed-meshheading:21474070-Quinoxalines,
pubmed-meshheading:21474070-Receptors, Adrenergic, beta,
pubmed-meshheading:21474070-Second Messenger Systems,
pubmed-meshheading:21474070-Sequence Homology, Amino Acid,
pubmed-meshheading:21474070-Thiazolidinediones
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110?.
|
|
pubmed:affiliation |
Department of Genetics, Biology and Biochemistry, Molecular Biotechnology Center, University of Torino, Torino 10126, Italy.
|
