SpringerProtocols: Abstract: 2. IκB Kinase and NF-κB Signaling in Response to Pro-Inflammatory Cytokines

2. IκB Kinase and NF-κB Signaling in Response to Pro-Inflammatory Cytokines

By: Mireille Delhase²

Abstract

Full Text

Download PDF (366K)

Exposure to pro-inflammatory cytokines (TNFα and IL-1) results in activation of signaling cascades that lead to stimulation of activity of the transcription factors AP-1 and NF-κB and induction of genes that are controlled by these transcription factors. Such genes code for cytokines (TNFα, IL-1, IL-2, IL-6, and GM-CSF), chemokines, adhesion molecules, and enzymes (iNOS and X-2) that produce secondary inflammatory mediators (1).

Affiliation(s): (2) University of California at San Diego, La Jolla, CA

Book Title: Inflammation Protocols

Series: Methods in Molecular Biology | Volume: 225 | Pub. Date: Apr-08-2003 | Page Range: 7-17 | DOI: 10.1385/1-59259-374-7:7

Subject: Immunology

References

Download References

1.	Barnes, P. J. and Karin, M. (1997) Nuclear factor-κB—A pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 15, 1066–1071.

2.	Baeuerle, P. A. and Baltimore, D. (1996) NF-kappa B: ten years after. Cell 87, 13–20.

3.	Ghosh, S., May, M. J., and Kopp, E. B. (1998) NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Ann. Rev. Immunol. 16, 225–260.

4.	Rothwarf, D. M. and Karin, M. (1999) The NF-κB activation pathway: a paradigm in information transfer from the membrane to the nucleus. Science’s STKE. www.stke.org/cgi/content/full/OC_sigtrans;1999/5/re1.

5.	Karin, M. and Delhase, M. (2000) The IκB kinase (IKK) and NF-κB: key elements of proinflammatory signalling. Sem. Immunol. 12, 85–98.

6.	Karin, M. and Ben-Neriah, Y. (2000) Phosphorylation meets ubiquitination: the control of NF-κB activity. Ann. Rev. Immunol. 18, 621–663.

7.	Delhase, M., Hayakawa, M., Chen, Y., and Karin, M. (1999) Positive and negative regulation of IκB kinase activity through IKKβ subunit phosphorylation. Science 284, 309–313.

8.	Li, Q., Van Antwerp, D., Mercurio, F., Lee, K.-F., and Verma, I. M. (1999) Severe liver degeneration in mice lacking the IκB kinase 2 gene. Science 284, 321–325.

9.	Li, Z.-W., Chu, W., Hu, Y., Delhase, M., Deerinck, T., Ellisman, M., Johnson, R. and Karin, M. (1999) The IKKβ subunit of IκB kinase (IKK) is essential for NF-κB activation and prevention of apoptosis. J. Exp. Med. 189, 839–1845.

10.	Yamaoka, S., Courtois, G., Bessia, C, Whiteside, S. T., Weil, R., Agou, F., et al. (1998) Complementation cloning of NEMO, a component of the IκB kinase complex essential for NF-κB activation. Cell 93, 1231–1240.

11.	Rothwarf, D. M., Zandi, E., Natoli, G., and Karin, M. (1998) IKKγ is an essential regulatory subunit of the I_B kinase complex. Nature 395, 297–300.

12.	Makris, C, Godfrey, V. L., Krahn-Senftleben, G., Takahashi, T., Roberts, J. L., Schwarz, T., et al. (2000) Female mice heterozygous for IKKγ/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti. Mol. Cell 5, 969–979.

13.	Hu, Y., Baud, V., Delhase, M., Zhang, P., Deerinck, T., Ellisman, M., et al. (1999) Abnormal morphogenesis but intact IKK activation in mice lacking the IKKα subunit of the IκB kinase. Science 284, 316–320.

14.	Takeda, K., Takeuchi, O., Tsujimura, T., Itami, S., Adachi, O., Kawai, T., et al. (1999) Limb and skin abnormalities in mice lacking IKKα. Science 284, 313–316.

15.	Senftleben, U., Cao, Y., Xiao, G., Greten, F. R., Krahn, G., Bonizzi, G., et al. (2001). Activation by IKKa of a second evolutionary conserved, NF-κB signaling pathway. Science 293, 1495–1499.

16.	Mercurio, F., DiDonato, J., Rosette, C, and Karin, M. (1992) Molecular cloning and characterization of a novel Rel/NF-κB family member displaying structural and functional homology to NF-κB p50/p105. DNA Cell Biol. 11, 523–537.

17.	Ausubel, F., Brent, R., Kingston, R.E., Moore, D. D., Smith, J. A., Seidman, J. G., et al., Eds. (1991) Current Protocols in Molecular Biology, Wiley, New York.

Comments (Loading...)

Post comment/View all comments