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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
49
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pubmed:dateCreated |
2000-2-3
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pubmed:abstractText |
Human immunodeficiency virus Nef plays an important role in AIDS pathogenesis. In addition to the well known down-regulation of cell surface receptors (CD4, MHCI), Nef is able to alter cellular signaling. Of particular interest for this study is the ability of Nef to bind with a very high affinity to SH3 domains of myelomonocyte-specific protein-tyrosine kinases of the Src family (Src-like PTK). We have therefore investigated Ca(2+) signaling in HL60 cells retrovirally transduced with wild type Nef or with a Nef mutant deficient in the SH3-interacting proline-rich motif (Nef((PXXP)4(-))). In differentiated HL60 cells, Nef markedly altered cellular Ca(2+) signaling; the amount of intracellularly stored Ca(2+) was increased, and as a consequence, store-operated Ca(2+)-influx was decreased. This effect was not observed in undifferentiated HL60 cells or in CEM T-lymphocytes and correlated with the differentiation-induced up-regulation of Src-like PTK. The Nef effect on Ca(2+) signaling depended entirely on the integrity of its PXXP motif. The Src-like PTK p56/59(hck) co-immunoprecipitated with both Nef and with the inositol 1,4,5-trisphosphate receptor, providing a possible mechanistic link between the viral protein and intracellular Ca(2+) stores of the host cell. Collectively, our results demonstrate that the human immunodeficiency virus 1 Nef protein manipulates intracellular Ca(2+) stores through SH3-mediated interactions in myelomonocytic 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/Calcitriol,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Dimethyl Sulfoxide,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, nef,
http://linkedlifedata.com/resource/pubmed/chemical/HCK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ionomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Ionophores,
http://linkedlifedata.com/resource/pubmed/chemical/N-Formylmethionine...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-hck,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/lyn protein-tyrosine kinase,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
34765-72
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:10574946-Calcitriol,
pubmed-meshheading:10574946-Calcium,
pubmed-meshheading:10574946-Calcium Channel Agonists,
pubmed-meshheading:10574946-Cell Differentiation,
pubmed-meshheading:10574946-Dimethyl Sulfoxide,
pubmed-meshheading:10574946-Down-Regulation,
pubmed-meshheading:10574946-Enzyme Inhibitors,
pubmed-meshheading:10574946-Gene Products, nef,
pubmed-meshheading:10574946-HL-60 Cells,
pubmed-meshheading:10574946-Humans,
pubmed-meshheading:10574946-Ionomycin,
pubmed-meshheading:10574946-Ionophores,
pubmed-meshheading:10574946-N-Formylmethionine Leucyl-Phenylalanine,
pubmed-meshheading:10574946-Protein Binding,
pubmed-meshheading:10574946-Protein-Tyrosine Kinases,
pubmed-meshheading:10574946-Proto-Oncogene Proteins,
pubmed-meshheading:10574946-Proto-Oncogene Proteins c-hck,
pubmed-meshheading:10574946-Signal Transduction,
pubmed-meshheading:10574946-Tetradecanoylphorbol Acetate,
pubmed-meshheading:10574946-Thapsigargin,
pubmed-meshheading:10574946-Time Factors,
pubmed-meshheading:10574946-Transfection,
pubmed-meshheading:10574946-src Homology Domains,
pubmed-meshheading:10574946-src-Family Kinases
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pubmed:year |
1999
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pubmed:articleTitle |
The HIV Nef protein alters Ca(2+) signaling in myelomonocytic cells through SH3-mediated protein-protein interactions.
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pubmed:affiliation |
Department of Morphology, Geneva Medical School, University of Geneva, CH-1225 Geneva, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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