Abstract
The requirements for the oncogenic conversion of the c-abl proto-oncogene have been determined by the expression of N-terminal deleted forms and viral gag-fused forms of the c-abl proteins from a selectable retroviral vector. To activate the transforming potential of c-abl, it is necessary that (i) specific N-terminal amino acids are deleted to release the kinase from negative regulation in vivo; (ii) an N-terminal myristylation site is part of the activated kinase; (iii) the fatty-acylated, activated kinase is overproduced. The N-terminal amino acids found to be necessary for the cellular inhibition of c-abl tyrosine phosphorylation are part of a homologous region present in many non-receptor tyrosine kinases, the v-crk oncogene and phospholipase C-II. Overproduction of a deregulated and myristylated c-abl tyrosine kinase induces the transformation of NIH 3T3 cells.
Publication types
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Comparative Study
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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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Abelson murine leukemia virus / genetics
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Amino Acid Sequence
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Cell Line
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Cell Transformation, Neoplastic / enzymology*
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Chromosome Deletion
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Enzyme Activation
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Fibroblasts
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Fusion Proteins, bcr-abl
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Gene Products, gag
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Moloney murine leukemia virus / genetics
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Neoplasm Proteins / physiology
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Phosphorylation
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Protein Processing, Post-Translational
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-abl
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Recombinant Fusion Proteins / metabolism
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Retroviridae Proteins / genetics
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Viral Proteins / physiology
Substances
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Gene Products, gag
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Retroviridae Proteins
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Viral Proteins
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Protein-Tyrosine Kinases
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Fusion Proteins, bcr-abl
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Proto-Oncogene Proteins c-abl