Abstract
The c-Jun NH(2)-terminal kinase (JNK) is activated when cells are exposed to environmental stress, including UV radiation. Gene disruption studies demonstrate that JNK is essential for UV-stimulated apoptosis mediated by the mitochondrial pathway by a Bax/Bak-dependent mechanism. Here, we demonstrate that JNK phosphorylates two members of the BH3-only subgroup of Bcl2-related proteins (Bim and Bmf) that are normally sequestered by binding to dynein and myosin V motor complexes. Phosphorylation by JNK causes release from the motor complexes. These proapoptotic BH3-only proteins therefore provide a molecular link between the JNK signal transduction pathway and the Bax/Bak-dependent mitochondrial apoptotic machinery.
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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Apoptosis Regulatory Proteins
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Apoptosis*
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Bcl-2-Like Protein 11
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Carrier Proteins / metabolism*
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Cell Line
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DNA Mutational Analysis
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DNA, Complementary / metabolism
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Fibroblasts / metabolism
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Humans
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Membrane Proteins*
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Mitochondria / metabolism
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Models, Biological
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Neurons / cytology
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Phosphorylation
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Plasmids / metabolism
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Protein Binding
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Protein Isoforms
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Signal Transduction
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Threonine / chemistry
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bcl-2-Associated X Protein
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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BAX protein, human
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BCL2L11 protein, human
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BMF protein, human
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Bcl-2-Like Protein 11
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Carrier Proteins
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DNA, Complementary
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Membrane Proteins
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Protein Isoforms
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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Threonine