Linked Life Data

9882708

Source:http://linkedlifedata.com/resource/pubmed/id/9882708

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-2-4
pubmed:abstractText
In cultured vascular smooth muscle cells (VSMCs), activation of phospholipase D (PLD) by angiotensin II (Ang II) represents a major source of sustained generation of second messengers. Understanding the molecular mechanisms controlling activation of this pathway is essential to clarify the complexities of Ang II signaling, but the most proximal mechanisms coupling AT1 receptors to PLD have not been defined. Here we examine the role of heterotrimeric G proteins in AT1 receptor-PLD coupling. In alpha-toxin permeabilized VSMCs, GTPgammaS enhanced Ang II-stimulated PLD activation. In intact cells, Ang II activation of PLD was pertussis toxin-insensitive and was not additive with sodium fluoride, a cell-permeant activator of heterotrimeric G proteins, indicating that AT1 receptor-PLD coupling requires pertussis toxin-insensitive heterotrimeric G proteins. Ang II-stimulated PLD activity was significantly inhibited in VSMCs electroporated with anti-Gbeta antibody (56 +/- 5%) and in cells overexpressing the Gbetagamma-binding region of the carboxyl terminus of beta-adrenergic receptor kinase1 (79 +/- 8%), suggesting a critical role for Gbetagamma in PLD activation by Ang II. This effect may be mediated by pp60(c-src), because in beta-adrenergic receptor kinase1 overexpressing cells, pp60(c-src) activation was inhibited, and in normal cells anti-pp60(c-src) antibody inhibited Ang II-stimulated PLD activity. Galpha12 may also contribute to AT1 receptor-PLD coupling because electroporation of anti-Galpha12 antibody significantly inhibited PLD activity, whereas anti-Galphai and Galphaq/11 antibodies had no effect. Furthermore, electroporation of anti-RhoA antibody also attenuated Ang II-induced PLD activation, suggesting a role for small molecular weight G protein RhoA in this response. Thus, we provide evidence here that Gbetagamma as well as Galpha12 subunits mediate AT1 receptor coupling to tonic PLD activation via pp60(c-src)-dependent mechanisms, and that RhoA is involved in these signaling pathways in rat VSMCs. These results may provide insight into the molecular mechanisms underlying the highly organized, complex, chronic signaling programs associated with vascular smooth muscle growth and remodeling in response to Ang II.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
142-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Angiotensin II receptor coupling to phospholipase D is mediated by the betagamma subunits of heterotrimeric G proteins in vascular smooth muscle cells.
pubmed:affiliation
Department of Medicine, Division of Cardiology, Emory University, Atlanta, Georgia, USA. mfukai@emory.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.