MAP Kinase Signaling

The stress-activated protein kinase/Jun-amino-terminal kinase SAPK/JNK is potently and preferentially activated by a variety of environmental stresses including UV and gamma radiation, ceramides, inflammatory cytokines and in some instances, by growth factors and GPCR agonists (1-6). As with the other MAPKs, the core signaling unit is composed of a MAPKKK, typically MEKK1-MEKK4, or by one of the mixed lineage kinases (MLKs), which phosphorylate and activate MKK4/7. Upon activation, MKKs phosphorylate and activate the SAPK/JNK kinase (2). Stress signals are delivered to this cascade by small GTPases of the Rho family (Rac, Rho, cdc42) (3). Both Rac1 and cdc42 mediate the stimulation of MEKKs and MLKs (3). Alternatively, MKK4/7 can be activated in a GTPase independent mechanism via stimulation of a germinal center kinase (GCK) family member (4). There are three SAPK/JNK genes each of which undergoes alternative splicing resulting in numerous isoforms (3). SAPK/JNK, when active as a dimer, can translocate to the nucleus and regulate transcription through its effects on c-Jun, ATF-2 and other transcription factors (3,5).

1. Davis, R.J. (1999) Biochem Soc Symp 64, 1-12.
2. Ichijo, H. (1999) Oncogene 18, 6087-93.
3. Kyriakis, J.M. and Avruch, J. (2001) Physiol Rev 81, 807-69.
4. Kyriakis, J.M. (1999) J Biol Chem 274, 5259-62.
5. Leppä, S. and Bohmann, D. (1999) Oncogene 18, 6158-62.
6. Whitmarsh, A.J. and Davis, R.J. (1998) Trends Biochem Sci 23, 481-5.

• Brouard, S. et al. (2000) Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J. Exp. Med. 192, 1015-1026. Applications: Western Blotting
• Park, Y. C. et al. (2000) A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Cell 101, 777-787. Applications: Western Blotting
• Chen, F. et al. (2001) Opposite effect of NF-kappa B and c-Jun N-terminal kinase on p53-independent GADD45 induction by arsenite. J. Biol. Chem. 276, 11414-11419. Applications: Western Blotting
• Hebert, S. S. et al. (2000) The mixed lineage kinase DLK is oligomerized by tissue transglutaminase during apoptosis. J. Biol. Chem. 275, 32482-32490. Applications: Western Blotting
• Xiao, G. G. et al. (2003) Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line. J. Biol. Chem. 278, 50781-50790. Applications: Western Blotting
• Banerjee, S. et al. (2002) Murine coronavirus replication-induced p38 mitogen-activated protein kinase activation promotes interleukin-6 production and virus replication in cultured cells. J. Virol. 76, 5937-5948. Applications: Western Blotting
• Dai, Y. et al. (2001) Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells. Cancer Res. 61, 5106-5115. Applications: Western Blotting
• Lee, E. G. et al. (2000) Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 289, 2350-2354. Applications: Western Blotting
• Turner, N.A. et al. (2009) Am J Physiol Heart Circ Physiol 297, H1117-27. Applications: Western Blotting
• Lal, H. et al. (2007) J Mol Cell Cardiol 43, 137-47. Applications: Western Blotting
• Wu, M. et al. (2009) Diabetes Metab Res Rev 25, 279-86. Applications: Western Blotting
• Lal, H. et al. (2008) J Mol Cell Cardiol 45, 770-8. Applications: Western Blotting
• Kojima, R. et al. (2004) Biochem J 380, 783-94. Applications: Western Blotting
• Tokunaga, F. et al. (2009) Nat Cell Biol 11, 123-32. Applications: Western Blotting
• Iwawaki, T. et al. (2009) Proc Natl Acad Sci U S A 106, 16657-62. Applications: Western Blotting

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SAPK/JNK Antibody

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