rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
Abelson murine leukemia virus (Ab-MLV) encodes the v-Abl protein tyrosine kinase and induces transformation of immortalized fibroblast lines and pre-B cells. Temperature-sensitive mutations affecting the kinase domain of the protein have demonstrated that the kinase activity is absolutely required for transformation. Despite this requirement, mutations affecting other regions of v-Abl modulate transformation activity. The SH2 domain and the highly conserved FLVRES motif within it form a phosphotyrosine-binding pocket that is required for interactions between the kinase and cellular substrates. To understand the impact of SH2 alterations on Ab-MLV-mediated transformation, we studied the Ab-MLV mutant P120/R273K. This mutant encodes a v-Abl protein in which the beta B5 arginine at the base of the phosphotyrosine-binding pocket has been replaced by a lysine. Unexpectedly, infection of NIH 3T3 or pre-B cells with P120/R273K revealed a temperature-dependent transformation phenotype. At 34 degrees C, P120/R273K transformed about 10-fold fewer cells than wild-type virus of equivalent titer; at 39.5 degrees C, 300-fold fewer NIH 3T3 cells were transformed and pre-B cells were refractory to transformation. Temperature-dependent transformation was accompanied by decreased phosphorylation of Shc, a protein that interacts with the v-Abl SH2 and links the protein to Ras, and decreased induction of c-Myc expression. These data suggest that alteration of the FLVRES pocket affects the ability of v-Abl to interact with at least some of its substrates in a temperature-dependent fashion and identify a novel type of temperature-sensitive Abelson virus.
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pubmed:grant |
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pubmed:commentsCorrections |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-538X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
75
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1816-23
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:11160680-3T3 Cells,
pubmed-meshheading:11160680-Abelson murine leukemia virus,
pubmed-meshheading:11160680-Animals,
pubmed-meshheading:11160680-B-Lymphocytes,
pubmed-meshheading:11160680-Cell Line, Transformed,
pubmed-meshheading:11160680-Cell Transformation, Viral,
pubmed-meshheading:11160680-Genes, Viral,
pubmed-meshheading:11160680-Mice,
pubmed-meshheading:11160680-Mutation,
pubmed-meshheading:11160680-Oncogene Proteins v-abl,
pubmed-meshheading:11160680-Precursor B-Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:11160680-Premenopause,
pubmed-meshheading:11160680-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:11160680-Signal Transduction,
pubmed-meshheading:11160680-Temperature,
pubmed-meshheading:11160680-ras Proteins,
pubmed-meshheading:11160680-src Homology Domains
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pubmed:year |
2001
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pubmed:articleTitle |
Temperature-sensitive transformation by an Abelson virus mutant encoding an altered SH2 domain.
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pubmed:affiliation |
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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