rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2008-9-4
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pubmed:abstractText |
Class IA phosphotidylinositol-3-kinases (PI3Ks) are a family of p85/p110 heterodimeric lipid kinases that are important in regulating signaling events in B and T cells. However, their role in natural killer (NK) cells is not understood. Here, using mice that lack the regulatory p85alpha subunit and its alternatively spliced variants p55alpha/p50alpha (collectively termed as p85alpha(-/-)), we defined the role of PI3K in NK cell development and function. p85alpha(-/-) mice had impaired lineage commitment leading to reduced NK cellularity in the bone marrow and liver. p85alpha(-/-) NK cells showed a defective Ly49 subset specification and a decreased expression of CD43. Lack of p85alpha severely reduced the NK-mediated cytotoxicity against tumor cells representing 'induced-self' and 'missing-self'. More importantly, NKG2D and NK1.1 receptor-mediated cytokine and chemokine generation was significantly compromised in p85alpha(-/-) NK cells. These results reveal a previously unrecognized role of p85alpha in the development, terminal maturation, cytokine/chemokine generation and tumor clearance of NK cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD43,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alphaV,
http://linkedlifedata.com/resource/pubmed/chemical/Klrk1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/NK Cell Lectin-Like Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Natural Killer Cell
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1476-5470
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
522-35
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18548087-Animals,
pubmed-meshheading:18548087-Antigens, CD43,
pubmed-meshheading:18548087-Bone Marrow,
pubmed-meshheading:18548087-Cell Differentiation,
pubmed-meshheading:18548087-Chemokines,
pubmed-meshheading:18548087-Cytokines,
pubmed-meshheading:18548087-Integrin alphaV,
pubmed-meshheading:18548087-Killer Cells, Natural,
pubmed-meshheading:18548087-Liver,
pubmed-meshheading:18548087-Mice,
pubmed-meshheading:18548087-NK Cell Lectin-Like Receptor Subfamily K,
pubmed-meshheading:18548087-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18548087-Receptors, Immunologic,
pubmed-meshheading:18548087-Receptors, Natural Killer Cell
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pubmed:year |
2008
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pubmed:articleTitle |
Deletion of PI3K-p85alpha gene impairs lineage commitment, terminal maturation, cytokine generation and cytotoxicity of NK cells.
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pubmed:affiliation |
Laboratory of Molecular Immunology, Blood Research Institute, Milwaukee, WI, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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