Abstract
The product of the c-abl gene is a non-receptor tyrosine kinase that is localized to the nucleus and cytoplasm. The precise function of c-Abl is unknown. Here we show that ionizing radiation activates c-Abl. Similar results were obtained with the alkylating agents cis-platinum and mitomycin C. We also demonstrate that cells deficient in c-Abl fail to activate Jun kinase (JNK/SAP kinase) after ionizing radiation or alkylating agent exposure and that reconstitution of c-Abl in these cells restores that response. In contrast, the stress response to tumour-necrosis factor is stimulated by a c-Abl-independent mechanism. These findings indicate that c-abl is involved in the stress response to DNA-damaging agents.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Cell Line
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Cisplatin / pharmacology
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DNA / drug effects*
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DNA / metabolism
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DNA Damage*
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Enzyme Activation
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Humans
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JNK Mitogen-Activated Protein Kinases*
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MAP Kinase Kinase 4
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Mice
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Mitogen-Activated Protein Kinase Kinases*
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Mitomycins / pharmacology
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Molecular Sequence Data
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Peptides / metabolism
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Protein Kinases / metabolism
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Protein-Tyrosine Kinases / radiation effects
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Proto-Oncogene Proteins c-abl / genetics
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Proto-Oncogene Proteins c-abl / metabolism*
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Proto-Oncogene Proteins c-abl / radiation effects
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Proto-Oncogene Proteins c-jun / metabolism
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Radiation, Ionizing
Substances
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Mitomycins
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Peptides
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Proto-Oncogene Proteins c-jun
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DNA
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Protein Kinases
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Protein-Tyrosine Kinases
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Proto-Oncogene Proteins c-abl
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases
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Cisplatin