This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bogoyevitch, M. A. Articles by Kobe, B. Search for Related Content PubMed PubMed Citation Articles by Bogoyevitch, M. A. Articles by Kobe, B.

Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases

Cell Signalling Laboratory, Biochemistry and Molecular Biology, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Crawley, Australia,¹ School of Molecular and Microbial Sciences, Institute for Molecular Bioscience and Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane, Australia²

The c-Jun N-terminal kinases (JNKs) are members of a larger group of serine/threonine (Ser/Thr) protein kinases from the mitogen-activated protein kinase family. JNKs were originally identified as stress-activated protein kinases in the livers of cycloheximide-challenged rats. Their subsequent purification, cloning, and naming as JNKs have emphasized their ability to phosphorylate and activate the transcription factor c-Jun. Studies of c-Jun and related transcription factor substrates have provided clues about both the preferred substrate phosphorylation sequences and additional docking domains recognized by JNK. There are now more than 50 proteins shown to be substrates for JNK. These include a range of nuclear substrates, including transcription factors and nuclear hormone receptors, heterogeneous nuclear ribonucleoprotein K, and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Many nonnuclear substrates have also been characterized, and these are involved in protein degradation (e.g., the E3 ligase Itch), signal transduction (e.g., adaptor and scaffold proteins and protein kinases), apoptotic cell death (e.g., mitochondrial Bcl2 family members), and cell movement (e.g., paxillin, DCX, microtubule-associated proteins, the stathmin family member SCG10, and the intermediate filament protein keratin 8). The range of JNK actions in the cell is therefore likely to be complex. Further characterization of the substrates of JNK should provide clearer explanations of the intracellular actions of the JNKs and may allow new avenues for targeting the JNK pathways with therapeutic agents downstream of JNK itself.

This article has been cited by other articles:

• Endo, Y., Beauchamp, E., Woods, D., Taylor, W. G., Toretsky, J. A., Uren, A., Rubin, J. S. (2008). Wnt-3a and Dickkopf-1 Stimulate Neurite Outgrowth in Ewing Tumor Cells via a Frizzled3- and c-Jun N-Terminal Kinase-Dependent Mechanism. Mol. Cell. Biol. 28: 2368-2379 [Abstract] [Full Text]  
• Shintani, Y., Fukumoto, Y., Chaika, N., Svoboda, R., Wheelock, M. J., Johnson, K. R. (2008). Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1. J. Cell Biol. 180: 1277-1289 [Abstract] [Full Text]  
• Nair, R. R., Avila, H., Ma, X., Wang, Z., Lennartz, M., Darnay, B. G., Boyd, D. D., Yan, C. (2008). A Novel High-Throughput Screening System Identifies a Small Molecule Repressive for Matrix Metalloproteinase-9 Expression. Mol. Pharmacol. 73: 919-929 [Abstract] [Full Text]  
• Witte, H., Neukirchen, D., Bradke, F. (2008). Microtubule stabilization specifies initial neuronal polarization. J. Cell Biol. 180: 619-632 [Abstract] [Full Text]  
• Farmer, J. L., Burghardt, R. C., Jousan, F. D., Hansen, P. J., Bazer, F. W., Spencer, T. E. (2008). Galectin 15 (LGALS15) functions in trophectoderm migration and attachment. FASEB J. 22: 548-560 [Abstract] [Full Text]  
• Takatori, A., Geh, E., Chen, L., Zhang, L., Meller, J., Xia, Y. (2008). Differential transmission of MEKK1 morphogenetic signals by JNK1 and JNK2. Development 135: 23-32 [Abstract] [Full Text]  
• Salojin, K., Oravecz, T. (2007). Regulation of innate immunity by MAPK dual-specificity phosphatases: knockout models reveal new tricks of old genes. J. Leukoc. Biol. 81: 860-869 [Abstract] [Full Text]