A new c-Jun N-terminal kinase (JNK)-interacting protein, Sab (SH3BP5), associates with mitochondria

We have identified a novel c-Jun N-terminal kinase (JNK)-interacting protein, Sab, by yeast two-hybrid screening. Sab binds to and serves as a substrate for JNK in vitro, and was previously found to interact with the Src homology 3 (SH3) domain of Bruton's tyrosine kinase (Btk). Inspection of t...

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Bibliographic Details
Published in:Biochemical journal 2002-11, Vol.367 (Pt 3), p.577-585
Main Authors: Wiltshire, Carolyn, Matsushita, Masato, Tsukada, Satoshi, Gillespie, David A F, May, Gerhard H W
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Animals
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Line, Transformed
Chick Embryo
JNK Mitogen-Activated Protein Kinases
Mitochondria - metabolism
Mitogen-Activated Protein Kinases - metabolism
Mutagenesis, Site-Directed
Signal Transduction
Substrate Specificity
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Summary:We have identified a novel c-Jun N-terminal kinase (JNK)-interacting protein, Sab, by yeast two-hybrid screening. Sab binds to and serves as a substrate for JNK in vitro, and was previously found to interact with the Src homology 3 (SH3) domain of Bruton's tyrosine kinase (Btk). Inspection of the sequence of Sab reveals the presence of two putative mitogen-activated protein kinase interaction motifs (KIMs) similar to that found in the JNK docking domain of the c-Jun transcription factor, and four potential serine-proline JNK phosphorylation sites in the C-terminal half of the molecule. Using deletion and site-directed mutagenesis, we demonstrate that the most N-terminal KIM in Sab is essential for JNK binding, and that, as with c-Jun, physical interaction with JNK is necessary for Sab phosphorylation. Interestingly, confocal immunocytochemistry and cell fractionation studies indicate that Sab is associated with mitochondria, where it co-localizes with a fraction of active JNK. These and previously reported properties of Sab suggest a possible role in targeting JNK to this subcellular compartment and/or mediating cross-talk between the Btk and JNK signal transduction pathways.
ISSN:0264-6021
1470-8728
DOI:10.1042/BJ20020553