Abstract
A complementation strategy was developed to define the signaling pathways activated by the Bcr-Abl tyrosine kinase. Transformation inactive point mutants of Bcr-Abl were tested for complementation with c-Myc. Single point mutations in the Src-homology 2 (SH2) domain, the major tyrosine autophosphorylation site of the kinase domain, and the Grb-2 binding site in the Bcr region impaired the transformation of fibroblasts by Bcr-Abl. Hyperexpression of c-Myc efficiently restored transformation activity only to the Bcr-Abl SH2 mutant. These data support a model in which Bcr-Abl activates at least two independent pathways for transformation. This strategy may be useful for discerning signaling pathways activated by other oncogenes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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Cell Line
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Cell Transformation, Neoplastic*
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Fusion Proteins, bcr-abl / genetics*
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Fusion Proteins, bcr-abl / physiology
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GRB2 Adaptor Protein
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Gene Expression
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Genes, abl*
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Genes, myc*
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Genetic Complementation Test
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Molecular Sequence Data
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Phosphorylation
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Point Mutation
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Proteins / metabolism
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / physiology
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Rats
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Retroviridae / physiology
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Signal Transduction
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Transfection
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Tyrosine / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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GRB2 Adaptor Protein
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Grb2 protein, rat
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Proteins
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Proto-Oncogene Proteins c-myc
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Tyrosine
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Fusion Proteins, bcr-abl