Linked Life Data

8871656

Source:http://linkedlifedata.com/resource/pubmed/id/8871656

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1996-12-17
pubmed:abstractText
The mouse Nramp1 gene (Bcg/Ity/Lsh) controls innate defense to infection with intracellular parasites such as Mycobacterium, Salmonella, and Leishmania. Sequence analysis of Nramp1 predicts a hydrophobic, membrane-associated protein expressed exclusively in monocyte/macrophage lineages. A single G169D substitution within the fourth predicted transmembrane domain of Nramp1 is associated with susceptibility to infection (Bcg) in inbred mouse strains. To initiate the biochemical characterization of the Nramp1 protein and to analyze the molecular basis of susceptibility associated with the Nramp1(D169) allele, oligopeptides derived from Nramp1 and two fusion proteins containing the first 54 and the last 35 residues of Nramp1 were used to raise specific anti-Nramp1 antisera. In addition, a c-Myc epitope (EQKLISEEDL) was introduced in-frame at the C terminus of Nramp1 to follow its expression in a yeast heterologous system. Western analysis of crude membrane fractions from yeast demonstrated that Nramp1 is indeed an integral membrane protein (resistant to urea extraction). In resident Bcg(r) (129sv, Nramp1(G169)) macrophages, one of the anti-Nramp1 antisera identified by immunoprecipitation a protein of 90,000 to 100,000 apparent m.w. that was absent in macrophages from knockout mice bearing a null mutation at Nramp1. The Nramp1 protein could be metabolically labeled with orthophosphate and was sensitive to glycosylase treatment, verifying that Nramp1 is an integral membrane phosphoglycoprotein. Parallel analysis of macrophage extracts from Bcg(s) mouse strains (C57BL6/J and BALB/c, Nramp1(D169)) failed to detect mature Nrampl protein in these cells, suggesting that the G169D mutation at Nramp1 prevents proper maturation or membrane integration of the protein, resulting in its rapid degradation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
157
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3559-68
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8871656-Amino Acid Sequence, pubmed-meshheading:8871656-Animals, pubmed-meshheading:8871656-Antibodies, pubmed-meshheading:8871656-Base Sequence, pubmed-meshheading:8871656-Carrier Proteins, pubmed-meshheading:8871656-Cation Transport Proteins, pubmed-meshheading:8871656-DNA, Complementary, pubmed-meshheading:8871656-Genes, myc, pubmed-meshheading:8871656-Glycosylation, pubmed-meshheading:8871656-Immunity, Innate, pubmed-meshheading:8871656-Immunization, pubmed-meshheading:8871656-Leishmania, pubmed-meshheading:8871656-Macrophages, Peritoneal, pubmed-meshheading:8871656-Membrane Proteins, pubmed-meshheading:8871656-Mice, pubmed-meshheading:8871656-Mice, Inbred Strains, pubmed-meshheading:8871656-Molecular Sequence Data, pubmed-meshheading:8871656-Mutation, pubmed-meshheading:8871656-Mycobacterium, pubmed-meshheading:8871656-Phosphorylation, pubmed-meshheading:8871656-Recombinant Fusion Proteins, pubmed-meshheading:8871656-Saccharomyces cerevisiae, pubmed-meshheading:8871656-Salmonella
pubmed:year
1996
pubmed:articleTitle
Natural resistance to intracellular infections: Nramp1 encodes a membrane phosphoglycoprotein absent in macrophages from susceptible (Nramp1 D169) mouse strains.
pubmed:affiliation
McGill Center for the Study of Host Resistance, Montreal General Hospital, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't