Linked Life Data

21111809

Source:http://linkedlifedata.com/resource/pubmed/id/21111809

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-12-27
pubmed:abstractText
?-adrenoceptors (?AR) play a central role in the regulation of cAMP synthesis and cardiac contractility. Nucleoside diphosphate kinase B (NDPK B) regulates cAMP signalling by complex formation with G?? dimers thereby activating and stabilizing heterotrimeric G(s) proteins, key transducer of ?AR signals into the cell. Here, we explored the requirement of NDPK B for basal and ?AR-stimulated cAMP synthesis and analysed the underlying mechanisms by comparing wild-type NDPK B (WT) and its catalytically inactive H118N mutant. Stable overexpression of both WT- and H118N-NDPK B in cardiomyocyte derived H10 cells increased the plasma membrane content of G(s) and caveolin-1 and thus enhanced the isoproterenol (ISO)-stimulated cAMP-synthesis by about 2-fold. Conversely, the loss of NDPK B in embryonic fibroblasts from NDPK A/B-depleted mice was associated with a severe reduction in membranous G(s) protein and carveolin-1 content causing a marked decrease in basal and ISO-induced cAMP formation. Re-expression of NDPK B, but not of NDPK A, was able to rescue this phenotype. Both, re-expression of WT- and H118N-NDPK B induced the re-appearance of G(s) and caveolin-1 at the plasma membrane to a similar extent. Accordingly, WT- and H118N-NDPK B similarly enhanced ISO-induced cAMP formation. In contrast, the catalytically inactive H118N-NDPK B was less potent and less effective in rescuing basal cAMP production. Identical results were obtained in neonatal rat cardiac myocytes after siRNA-induced knockdown and adenoviral re-expression of NDPK B. Our data reveal that NDPK B regulates G(s) function by two different mechanisms. The complex formation of NDPK B with G(s) is required for the stabilization of the G protein content at the plasma membrane. In addition, the NDPK B-dependent phosphotransfer reaction, which requires the catalytic activity, specifically allows a receptor-independent, basal G(s) activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1873-3913
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
579-85
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Through scaffolding and catalytic actions nucleoside diphosphate kinase B differentially regulates basal and ?-adrenoceptor-stimulated cAMP synthesis.
pubmed:affiliation
Department of Internal Medicine III - Cardiology, University of Heidelberg, INF 410, D-69120 Heidelberg, Germany. hans-joerg.hippe@med.uni-heidelberg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't