Linked Life Data

15123679

Source:http://linkedlifedata.com/resource/pubmed/id/15123679

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2004-7-19
pubmed:abstractText
The P2X(7) receptor is a ligand-gated channel that is highly expressed on mononuclear cells of the immune system and that mediates ATP-induced apoptosis. Wide variations in the function of the P2X receptor have been observed, explained in part by (7)loss-of-function polymorphisms that change Glu(496) to Ala (E496A) and Ile(568) to Asn (I568N). In this study, a third polymorphism, which substitutes an uncharged glutamine for the highly positively charged Arg(307) (R307Q), has been found in heterozygous dosage in 12 of 420 subjects studied. P2X(7) function was measured by ATP-induced fluxes of Rb(+), Ba(2+), and ethidium(+) into peripheral blood monocytes or various lymphocyte subsets and was either absent or markedly decreased. Transfection experiments showed that P2X(7) carrying the R307Q mutation lacked either channel or pore function despite robust protein synthesis and surface expression of the receptor. The monoclonal antibody (clone L4) that binds to the extracellular domain of wild type P2X(7) and blocks P2X(7) function failed to bind to the R307Q mutant receptor. Differentiation of monocytes to macrophages up-regulated P2X(7) function in cells heterozygous for the R307Q to a value 10-40% of that for wild type macrophages. However, macrophages from a subject who was double heterozygous for R307Q/I568N remained totally non-functional for P2X(7), and lymphocytes from the same subject also lacked ATP-stimulated phospholipase D activity. These data identify a third loss-of-function polymorphism affecting the human P2X(7) receptor, and since the affected Arg(307) is homologous to those amino acids essential for ATP binding to P2X(1) and P2X(2), it is likely that this polymorphism abolishes the binding of ATP to the extracellular domain of P2X(7).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31287-95
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15123679-Adenosine Triphosphate, pubmed-meshheading:15123679-Amino Acid Substitution, pubmed-meshheading:15123679-Animals, pubmed-meshheading:15123679-Barium, pubmed-meshheading:15123679-Base Sequence, pubmed-meshheading:15123679-Binding Sites, pubmed-meshheading:15123679-Cell Line, pubmed-meshheading:15123679-DNA Primers, pubmed-meshheading:15123679-Female, pubmed-meshheading:15123679-Heterozygote, pubmed-meshheading:15123679-Humans, pubmed-meshheading:15123679-Ion Transport, pubmed-meshheading:15123679-Leukocytes, pubmed-meshheading:15123679-Macrophages, pubmed-meshheading:15123679-Oocytes, pubmed-meshheading:15123679-Phospholipase D, pubmed-meshheading:15123679-Polymorphism, Single Nucleotide, pubmed-meshheading:15123679-Receptors, Purinergic P2, pubmed-meshheading:15123679-Receptors, Purinergic P2X7, pubmed-meshheading:15123679-Recombinant Proteins, pubmed-meshheading:15123679-Transfection, pubmed-meshheading:15123679-Xenopus laevis
pubmed:year
2004
pubmed:articleTitle
An Arg307 to Gln polymorphism within the ATP-binding site causes loss of function of the human P2X7 receptor.
pubmed:affiliation
Department of Medicine, University of Sydney at Nepean Hospital, Penrith, New South Wales 2750, Australia.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't