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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
29
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pubmed:dateCreated |
1997-8-18
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pubmed:abstractText |
Tyrosine kinases of the Src family are regulated via their Src homology 2 (SH2) and SH3 domains. The Nef protein of human immunodeficiency virus-1 (HIV-1) has previously been shown to bind with high affinity and specificity in vitro to the SH3 domain of Hck, a Src family member expressed primarily in myeloid cells. However, the effect of Nef on Hck activity in living cells is unknown. Here we show that Rat-2 fibroblasts co-expressing Hck and Nef rapidly developed transformed foci, whereas control cells expressing either protein alone did not. Nef formed a stable complex with Hck and stimulated its tyrosine kinase activity in vivo. Mutagenesis of the Nef proline-rich motif essential for SH3 binding completely blocked complex formation, kinase activation, and transformation, indicating that the Nef SH3-binding function is required for its effects on Hck. These results provide direct evidence that SH3 engagement is sufficient to activate a Src family kinase in vivo and suggest that Hck may be activated by Nef in HIV-infected macrophages.
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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/Gene Products, nef,
http://linkedlifedata.com/resource/pubmed/chemical/HCK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hck protein, rat,
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/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/nef Gene Products, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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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 |
18
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17899-902
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9218412-Animals,
pubmed-meshheading:9218412-Cell Line,
pubmed-meshheading:9218412-Cell Transformation, Neoplastic,
pubmed-meshheading:9218412-Fibroblasts,
pubmed-meshheading:9218412-Gene Products, nef,
pubmed-meshheading:9218412-Genetic Vectors,
pubmed-meshheading:9218412-HIV-1,
pubmed-meshheading:9218412-Humans,
pubmed-meshheading:9218412-Mutagenesis, Site-Directed,
pubmed-meshheading:9218412-Phosphorylation,
pubmed-meshheading:9218412-Protein-Tyrosine Kinases,
pubmed-meshheading:9218412-Proto-Oncogene Proteins,
pubmed-meshheading:9218412-Proto-Oncogene Proteins c-hck,
pubmed-meshheading:9218412-Rats,
pubmed-meshheading:9218412-Recombinant Proteins,
pubmed-meshheading:9218412-Retroviridae,
pubmed-meshheading:9218412-nef Gene Products, Human Immunodeficiency Virus,
pubmed-meshheading:9218412-src Homology Domains
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pubmed:year |
1997
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pubmed:articleTitle |
SH3-mediated Hck tyrosine kinase activation and fibroblast transformation by the Nef protein of HIV-1.
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pubmed:affiliation |
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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