Linked Life Data

17626895

Source:http://linkedlifedata.com/resource/pubmed/id/17626895

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-8-31
pubmed:abstractText
Voltage-dependent Ca(2+) channel function (Ca(v)1.2, L-type Ca(2+) channel) is required for cardiac excitation-contraction (E-C) coupling. Ca(v)1.2 plays a key role in modulating cardiac function in response to classic signaling pathways, such as the renin-angiotensin system and sympathetic nervous system. Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with Ca(v)1.2 current through the actions of cAMP and cGMP. Cardiac cGMP, which activates protein kinase G (PKG), is regulated by nitric oxide (NO), and natriuretic peptides. Although PKG has been reported to activate or inhibit Ca(v)1.2 function, it is still unclear whether Ca(v)1.2 subunits are PKG substrates. We have identified phosphorylation sites within the alpha(1c) and beta(2a) subunits that are phosphorylated by PKGIalpha in vitro. We demonstrate that a subset of these phosphorylation sites is modulated, in a cGMP-PKG-specific manner, in intact HEK cells heterologously expressing alpha(1c) and beta(2a) subunits. Using phospho-epitope-specific antibodies, we show that the phosphorylation of these residues is enhanced by PKG in intact cardiac myocytes. Activation of PKG in HEK cells transfected with alpha(1c) and beta(2a) subunits caused an inhibition of Ca(v)1.2 whole-cell current. PKG-mediated inhibition of Ca(v)1.2 current was significantly reduced by coexpression of an alanine-substituted Ca(v)1.2 beta(2a) subunit (Ser(496)). Our results identify a molecular mechanism by which cGMP-PKG regulates Ca(v)1.2 phosphorylation and function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
31
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
465-74
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Protein kinase G phosphorylates Cav1.2 alpha1c and beta2 subunits.
pubmed:affiliation
Division of Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural