Linked Life Data

12671732

Source:http://linkedlifedata.com/resource/pubmed/id/12671732

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-4-2
pubmed:abstractText
Cell-mediated immunity (CMI) plays an essential role in human host defense against intracellular bacteria. Type-1 cytokines, particularly gamma interferon (IFN-gamma), interleukin-12 (IL-12), and IL-23, the major cytokines that regulate IFN-gamma production, are essential in CMI. This is illustrated by patients with unusual severe infections caused by poorly pathogenic mycobacteria and Salmonella species, in whom genetic deficiencies have been identified in several key genes in the type-1 cytokine pathway, including IL12RB1, the gene encoding the beta1 chain of the IL-12 and IL-23 receptors. Several mutations in IL12RB1 with deleterious effects on human IL-12R function have been identified, including nonsense and missense mutations. In addition, a number of coding IL12RB1 polymorphisms have been reported. In order to gain more insight into the effect that IL12RB1 mutations and genetic variations can have on IL-12Rbeta1 function, three approaches have been followed. First, we determined the degree of conservation at the variant amino acid positions in IL-12Rbeta1 between different species, using known deleterious mutations, known variations in IL-12Rbeta1, as well as novel coding variations that we have identified at position S74R and R156H. Second, we analyzed the potential impact of these amino acid variations on the three-dimensional structure of the IL-12Rbeta1 protein. Third, we analyzed the putative functions of different IL-12Rbeta1 domains, partly based on their homology with gp130, and analyzed the possible effects of the above amino acid variations on the function of these domains. Based on these analyses, we propose an integrated model of IL-12Rbeta1 structure and function. This significantly enhances our molecular understanding of the human IL-12 and IL-23 systems.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0093-7711
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
817-29
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12671732-Alternative Splicing, pubmed-meshheading:12671732-Amino Acid Sequence, pubmed-meshheading:12671732-Animals, pubmed-meshheading:12671732-Base Sequence, pubmed-meshheading:12671732-Genetic Variation, pubmed-meshheading:12671732-Humans, pubmed-meshheading:12671732-Interleukin-12, pubmed-meshheading:12671732-Interleukin-23, pubmed-meshheading:12671732-Interleukin-23 Subunit p19, pubmed-meshheading:12671732-Interleukins, pubmed-meshheading:12671732-Models, Immunological, pubmed-meshheading:12671732-Molecular Sequence Data, pubmed-meshheading:12671732-Mutation, pubmed-meshheading:12671732-Protein Structure, Tertiary, pubmed-meshheading:12671732-RNA, Messenger, pubmed-meshheading:12671732-Receptors, Interleukin, pubmed-meshheading:12671732-Receptors, Interleukin-12, pubmed-meshheading:12671732-Sequence Homology, Amino Acid, pubmed-meshheading:12671732-Species Specificity
pubmed:year
2003
pubmed:articleTitle
Genetic variations in the interleukin-12/interleukin-23 receptor (beta1) chain, and implications for IL-12 and IL-23 receptor structure and function.
pubmed:affiliation
Department of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't