Sab (SH3BP5), a novel mitochondria-localized JNK-interacting protein.
The JNK (c-Jun N-terminal kinase) pathway is activated by diverse stresses and can have an effect on a number of different cellular processes. Protein-protein interactions are critical for efficient signalling from JNK to multiple targets; through a screen for interacting proteins, we identified a novel JNK-interacting protein, Sab (SH3BP5). Sab has previously been found to interact with the Src homology 3 domain of Bruton's tyrosine kinase; however, the interaction with JNK occurs through a mitogen-activated protein KIM (kinase interaction motif) in a region distinct from the Bruton's tyrosine kinase-binding domain. As with c-Jun, the presence of this KIM is essential for Sab to act as a JNK substrate. Interestingly, Sab is associated with the mitochondria and co-localizes with a portion of active JNK after stress treatment. The present study and previously reported work may suggest a possible role for Sab in targeting JNK to this subcellular compartment and/or mediating crosstalk between different signal-transduction pathways.
Wiltshire
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IBLS Division of Biochemistry and Molecular Biology, University of Glasgow, Davidson Building, Glasgow G12 8QQ, UK. c.wiltshire@beatson.gla.ac.uk
Gillespie
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May
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D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002642:Chick Embryo; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007700:Kinetics; D048670:MAP Kinase Kinase 4; D008928:Mitochondria / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; C112230:SH3BP5 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases