The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Differential regulation of IκB kinase α and β by two upstream kinases, NF-κB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase-1
Open accessAbstract
NF-κB is activated by various stimuli including inflammatory cytokines and stresses. A key step in the activation of NF-κB is the phosphorylation of its inhibitors, IκBs, by an IκB kinase (IKK) complex. Recently, two closely related kinases, designated IKKα and IKKβ, have been identified to be the components of the IKK complex that phosphorylate critical serine residues of IκBs for degradation. A previously identified NF-κB-inducing kinase (NIK), which mediates NF-κB activation by TNFα and IL-1, has been demonstrated to activate IKKα. Previous studies showed that mitogen-activated protein kinase/ERK kinase kinase-1 (MEKK1), which constitutes the c-Jun N-terminal kinase/stress-activated protein kinase pathway, also activates NF-κB by an undefined mechanism. Here, we show that overexpression of MEKK1 preferentially stimulates the kinase activity of IKKβ, which resulted in phosphorylation of IκBs. Moreover, a catalytically inactive mutant of IKKβ blocked the MEKK1-induced NF-κB activation. By contrast, overexpression of NIK stimulates kinase activities of both IKKα and IKKβ comparably, suggesting a qualitative difference between NIK- and MEKK1-mediated NF-κB activation pathways. Collectively, these results indicate that NIK and MEKK1 independently activate the IKK complex and that the kinase activities of IKKα and IKKβ are differentially regulated by two upstream kinases, NIK and MEKK1, which are responsive to distinct stimuli.
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Cites
Function and Activation of NF-kappaB in the Immune System
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A cytokine-responsive IκB kinase that activates the transcription factor NF-κB
DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E., & Karin, M. (1997) · Nature · doi:10.1038/41493 · Cited by 2,125
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Cited by
Sanlioglu, S., Williams, C. M., Samavati, L., Butler, N. S., Wang, G., McCray, P. B., Ritchie, T. C., Hunninghake, G. W., Zandi, E., & Engelhardt, J. F. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102061200 · Cited by 395
ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway
Kopp, E., Medzhitov, R., Carothers, J., Xiao, C., Douglas, I., Janeway, C. A., & Ghosh, S. (1999) · Genes & Development · doi:10.1101/gad.13.16.2059 · Cited by 334
Tada, K., Okazaki, T., Sakon, S., Kobarai, T., Kurosawa, K., Yamaoka, S., Hashimoto, H., Mak, T. W., Yagita, H., Okumura, K., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104837200 · Cited by 306
Self-citationLi, Q., & Engelhardt, J. F. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511153200 · Cited by 219
Anderson, H. D. I., Rahmutula, D., & Gardner, D. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309552200 · Cited by 186
Sylla, B. S., Hung, S. C., Davidson, D. M., Hatzivassiliou, E., Malinin, N. L., Wallach, D., Gilmore, T. D., Kieff, E., & Mosialos, G. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.10106 · Cited by 137
Zheng, C., Xiang, J., Hunter, T., & Lin, A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.41.28966 · Cited by 110
Kang, J. S., Yoon, Y. D., Han, M. H., Han, S.-B., Lee, K., Park, S.-K., & Kim, H. M. (2007) · International Immunopharmacology · doi:10.1016/j.intimp.2006.12.004 · Cited by 45
Proapoptotic regimes for HTLV-I-transformed cells: targeting Tax and the NF-κB pathway
Kfoury, Y., Nasr, R., Hermine, O., de Thé, H., & Bazarbachi, A. (2005) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401624 · Cited by 40
New treatment regimes for virus-induced exacerbations of asthma
Edwards, M. R., Kebadze, T., Johnson, M. W., & Johnston, S. L. (2006) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2005.09.005 · Cited by 30
Metadata
- Authors
- Nakano, H., Shindo, M., Sakon, S., Nishinaka, S., Mihara, M., Yagita, H., & Okumura, K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-03-31
- Volume
- 95
- Issue
- 7
- Pages
- 3537-3542
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1979634801
- Cited by
- 517
- References
- 3
- FWCI
- 25.45
- Type
- journal article
- Language
- en
- Open access
- green
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