Source:http://linkedlifedata.com/resource/pubmed/id/21430226
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
2011-4-20
|
| pubmed:abstractText |
Type I protein kinase A (PKA) is targeted to the TCR-proximal signaling machinery by the A-kinase anchoring protein ezrin and negatively regulates T cell immune function through activation of the C-terminal Src kinase. RI anchoring disruptor (RIAD) is a high-affinity competitor peptide that specifically displaces type I PKA from A-kinase anchoring proteins. In this study, we disrupted type I PKA anchoring in peripheral T cells by expressing a soluble ezrin fragment with RIAD inserted in place of the endogenous A-kinase binding domain under the lck distal promoter in mice. Peripheral T cells from mice expressing the RIAD fusion protein (RIAD-transgenic mice) displayed augmented basal and TCR-activated signaling, enhanced T cell responsiveness assessed as IL-2 secretion, and reduced sensitivity to PGE(2)- and cAMP-mediated inhibition of T cell function. Hyperactivation of the cAMP-type I PKA pathway is involved in the T cell dysfunction of HIV infection, as well as murine AIDS, a disease model induced by infection of C57BL/6 mice with LP-BM5, a mixture of attenuated murine leukemia viruses. LP-BM5-infected RIAD-transgenic mice resist progression of murine AIDS and have improved viral control. This underscores the cAMP-type I PKA pathway in T cells as a putative target for therapeutic intervention in immunodeficiency diseases.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
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| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
1
|
| pubmed:volume |
186
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
5119-30
|
| pubmed:meshHeading |
pubmed-meshheading:21430226-A Kinase Anchor Proteins,
pubmed-meshheading:21430226-Animals,
pubmed-meshheading:21430226-Blotting, Western,
pubmed-meshheading:21430226-Cell Separation,
pubmed-meshheading:21430226-Cytoskeletal Proteins,
pubmed-meshheading:21430226-Disease Models, Animal,
pubmed-meshheading:21430226-Female,
pubmed-meshheading:21430226-Flow Cytometry,
pubmed-meshheading:21430226-Fluorescent Antibody Technique,
pubmed-meshheading:21430226-Humans,
pubmed-meshheading:21430226-Immunoblotting,
pubmed-meshheading:21430226-Immunoprecipitation,
pubmed-meshheading:21430226-Male,
pubmed-meshheading:21430226-Mice,
pubmed-meshheading:21430226-Mice, Inbred C57BL,
pubmed-meshheading:21430226-Mice, Transgenic,
pubmed-meshheading:21430226-Murine Acquired Immunodeficiency Syndrome,
pubmed-meshheading:21430226-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21430226-Signal Transduction,
pubmed-meshheading:21430226-T-Lymphocytes,
pubmed-meshheading:21430226-Transfection
|
| pubmed:year |
2011
|
| pubmed:articleTitle |
Mice with disrupted type I protein kinase A anchoring in T cells resist retrovirus-induced immunodeficiency.
|
| pubmed:affiliation |
The Biotechnology Center of Oslo, University of Oslo, N-0317 Oslo, Norway.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|