MAP Kinase Signaling

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c-Jun is a member of the Jun Family containing c-Jun, JunB and JunD, and is a component of the transcription factor AP-1 (activator protein-1). AP-1 is composed of dimers of Fos, Jun and ATF family members and binds to and activates transcription at TRE/AP-1 elements (reviewed in 1). Extracellular signals including growth factors, chemokines and stress activate AP-1-dependent transcription. The transcriptional activity of c-Jun is regulated by phosphorylation at Ser63 and Ser73 through SAPK/JNK (reviewed in 2). Knock-out studies in mice have shown that c-Jun is essential for embryogenesis (3), and subsequent studies have demonstrated roles for c-Jun in various tissues and developmental processes including axon regeneration (4), liver regeneration (5) and T cell development (6). AP-1 regulated genes exert diverse biological functions including cell proliferation, differentiation, and apoptosis, as well as transformation, invasion and metastasis, depending on cell type and context (7-9). Other target genes regulate survival as well as hypoxia and angiogenesis (8,10). c-Jun has emerged as a promising therapeutic target for cancer, vascular remodeling, acute inflammation, as well as rheumatoid arthritis (11,12).

1. Jochum, W. et al. (2001) Oncogene 20, 2401-12.
2. Davis, R.J. (2000) Cell 103, 239-52.
3. Hilberg, F. et al. (1993) Nature 365, 179-81.
4. Raivich, G. et al. (2004) Neuron 43, 57-67.
5. Behrens, A. et al. (2002) EMBO J 21, 1782-90.
6. Riera-Sans, L. and Behrens, A. (2007) J Immunol 178, 5690-700.
7. Leppä, S. and Bohmann, D. (1999) Oncogene 18, 6158-62.
8. Shaulian, E. and Karin, M. (2002) Nat Cell Biol 4, E131-6.
9. Weiss, C. and Bohmann, D. (2004) Cell Cycle 3, 111-3.
10. Karamouzis, M.V. et al. (2007) Mol Cancer Res 5, 109-20.
11. Kim, S. and Iwao, H. (2003) J Pharmacol Sci 91, 177-81.
12. Dass, C.R. and Choong, P.F. (2008) Pharmazie 63, 411-4.

• Zhang, S. Q. et al. (2000) Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. Immunity 12, 301-311. Applications: Western Blot
• Lee, S. A. et al. (2001) Role of ATM in oxidative stress-mediated c-Jun phosphorylation in response to ionizing radiation and CdCl2. J. Biol. Chem. 276, 11783-11790. Applications: Western Blot
• Kleemann, R. et al. (2000) Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Nature 408, 211-216. Applications: Western Blot
• de Ruiter, N. D. et al. (2000) Ras-dependent regulation of c-Jun phosphorylation is mediated by the Ral guanine nucleotide exchange factor-Ral pathway. Mol. Cell. Biol. 20, 8480-8488. Applications: Western Blot
• Hou, N. et al. (2008) Endocrinology 149, 1654-65. Applications: Western Blotting
• Uehara, N. et al. (2006) Exp Eye Res 82, 488-95. Applications: Western Blotting

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Phospho-c-Jun (Ser63) II Antibody

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