Linked Life Data

18230714

Source:http://linkedlifedata.com/resource/pubmed/id/18230714

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-3-18
pubmed:abstractText
Hypertension is a leading risk factor for the development of cardiovascular disease. Data from human and animal studies suggest that RGS2, a potent inhibitor of G(q) signaling, is important for blood pressure regulation. Several RGS2 mutations in the Japanese population have been found to be associated with hypertension. The product of one of these alleles, R44H, is mutated within the amino terminal amphipathic alpha-helix domain, the region responsible for plasma membrane-targeting. The functional consequence of this mutation and its potential link to the development of hypertension, however, are not known. In this study, we showed that R44H was a weaker inhibitor of receptor-mediated G(q) signaling than wild-type RGS2. Confocal microscopy revealed that YFP-tagged R44H bound to the plasma membrane less efficiently than wild-type RGS2. R44 is one of the basic residues positioned to stabilize lipid bilayer interaction of the RGS2 amphipathic helix domain. Tryptophan fluorescence and circular dichroism studies of this domain showed that the R44H mutation prevented proper entrenchment of hydrophobic residues into the lipid bilayer without disrupting helix-forming capacity. Together, these data suggest that decreasing the side-chain length and flexibility at R44 prevented proper lipid bilayer association and function of RGS2. Finally, the R44H protein did not behave as a dominant-negative interfering mutant. Thus, our data are consistent with the notion that a R44H missense mutation in human RGS2 produces a hypomorphic allele that may lead to altered receptor-mediated G(q) inhibition and contribute to the development of hypertension in affected subjects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1037-43
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18230714-Alleles, pubmed-meshheading:18230714-Amino Acid Sequence, pubmed-meshheading:18230714-Cell Line, pubmed-meshheading:18230714-Cell Membrane, pubmed-meshheading:18230714-GTP-Binding Protein alpha Subunits, Gq-G11, pubmed-meshheading:18230714-Genes, Dominant, pubmed-meshheading:18230714-Humans, pubmed-meshheading:18230714-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:18230714-Hypertension, pubmed-meshheading:18230714-Lipid Bilayers, pubmed-meshheading:18230714-Liposomes, pubmed-meshheading:18230714-Models, Biological, pubmed-meshheading:18230714-Molecular Sequence Data, pubmed-meshheading:18230714-Mutant Proteins, pubmed-meshheading:18230714-Mutation, Missense, pubmed-meshheading:18230714-Phospholipids, pubmed-meshheading:18230714-Polymorphism, Single Nucleotide, pubmed-meshheading:18230714-Protein Structure, Secondary, pubmed-meshheading:18230714-Protein Structure, Tertiary, pubmed-meshheading:18230714-Protein Transport, pubmed-meshheading:18230714-RGS Proteins, pubmed-meshheading:18230714-Recombinant Fusion Proteins, pubmed-meshheading:18230714-Transfection
pubmed:year
2008
pubmed:articleTitle
The RGS2 gene product from a candidate hypertension allele shows decreased plasma membrane association and inhibition of Gq.
pubmed:affiliation
University of Toronto, Rm 3334 MSB, 1 King's College Circle, Toronto, ON, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't