NF-kappaB Signaling

Cyclooxygenase1 (Cox1) and cyclooxygenase2 (Cox2), family members with 60% homology in humans, catalyze prostaglandin production from arachidonic acid (1,2). Cox1 is expressed constitutively in most tissues, while Cox2 expression is induced by lipopolysaccaride (LPS) and peptoglycan (PGN) (3). PGN activates Ras, leading to phosphorylation of Raf at Ser338 and Erk 1/2 at Tyr204). The activation of MAP kinase signaling results in subsequent activation of IKKα/β, phosphorylation of IκB-α at Ser32/36) and NF-κB activation. Finally, activation of the transcription factor NF-κB is responsible for the induction of Cox2 expression (4). LPS and PGN induce the clinical manifestations of arthritis and bacterial infections, such as inflammation, fever and septic shock (5), making Cox2 a useful target for therapeutic anti-inflammatory drugs (3). Both Cox1 and Cox2 also play a role in the neuropathology of Alzheimer's disease by potentiating γ-secretase activity and β-amyloid generation (6).

1. Xie, W.L. et al. (1991) Proc Natl Acad Sci USA 88, 2692-6.
2. Vane, J.R. et al. (1998) Annu Rev Pharmacol Toxicol 38, 97-120.
3. O'Neill, G.P. et al. (1994) Mol Pharmacol 45, 245-54.
4. Chen, B.C. et al. (2004) J Biol Chem 279, 20889-97.
5. Wang, Q. et al. (2001) Infect Immun 69, 2270-6.
6. Qin, W. et al. (2003) J Biol Chem 278, 50970-7.

• Lee, J.K. et al. (2004) Proc Natl Acad Sci U S A 101, 8815-20. Applications: Western Blotting

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Cox2 Antibody

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