Abstract
The nuclear function of the c-Abl tyrosine kinase is not well understood. In order to identify nuclear substrates of Abl, we constructed a constitutively active and nuclear form of the protein. We found that active nuclear Abl efficiently phosphorylate c-Jun, a transcription factor not previously known to be tyrosine phosphorylated. After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl. Surprisingly, elevated levels of c-Jun activated nuclear Abl, resulting in activation of the JNK serine/threonine kinase. This phosphorylation circuit generates nuclear tyrosine phosphorylation and represents a reversal of previously known signalling models.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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Cell Nucleus / metabolism
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Enzyme Activation
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Humans
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JNK Mitogen-Activated Protein Kinases
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Mice
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Mitogen-Activated Protein Kinases / metabolism*
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Phosphorylation
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Proto-Oncogene Proteins c-abl / metabolism*
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Proto-Oncogene Proteins c-jun / chemistry
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Proto-Oncogene Proteins c-jun / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Software
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Substrate Specificity
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Transfection
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Tyrosine
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src Homology Domains
Substances
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Proto-Oncogene Proteins c-jun
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Recombinant Proteins
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Tyrosine
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Proto-Oncogene Proteins c-abl
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases