International Immunology

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (151) Request Permissions Google Scholar Articles by Shimada, T. Articles by Akira, S. Search for Related Content PubMed PubMed Citation Articles by Shimada, T. Articles by Akira, S. Social Bookmarking          What's this?

International Immunology, Vol. 11, No. 8, 1357-1362, August 1999
© 1999 Japanese Society for Immunology

IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IB kinases

Takahiro Shimada^1,2,4, Taro Kawai^1,2,5, Kiyoshi Takeda^1,2,5, Makoto Matsumoto^1,2,5, Jun-ichiro Inoue³, Yoichi Tatsumi⁴, Akihisa Kanamaru⁴ and Shizuo Akira^1,2,5

¹ Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
² CREST of Japan Science and Technology Corporation, Japan
³ Department of Oncology, Institute of Medical Science, University of Tokyo, 1-6-4 Shiroganedai, Minatoku, Tokyo 108, Japan
⁴ Third Department of Internal Medicine, School of Medicine, Kinki University, 2-377 Ohono higashi, Osaka-Sayama, Osaka 589-0014, Japan

Correspondence to: S. Akira

	Abstract

Top Abstract Introduction References

 
Using the suppression subtractive hybridization technique, we isolated a novel kinase, IKK-i, whose message is drastically induced by lipopolysaccharide (LPS) in the mouse macrophage cell line RAW264.7. The predicted protein contains the kinase domain in its N-terminus, which shares 30% identity to that of IKK- or IKK-ß. The C-terminal portion contains a leucine zipper and a potential helix-loop-helix domain, as in the case of IKK- and IKK-ß. IKK-i is expressed mainly in immune cells, and is induced in response to proinflammatory cytokines such as tumor necrosis factor-, IL-1 and IL-6, in addition to LPS. Overexpression of wild-type IKK-i phosphorylated serine residues Ser32 and Ser36 of IB- (preferentially Ser36), and significantly stimulated NF-B activation. These results suggest that IKK-i is an inducible IB kinase which may play a special role in the immune response.

Keywords: IB kinase, inflammation, lipopolysaccharide, macrophage, NF-B

	Introduction

Top Abstract Introduction References

 
NF-B plays an important role in the regulation of a variety of genes involved in immune, acute phase and inflammatory responses. The active form of NF-B is composed of homo- and heterodimers of the NF-B/Rel family members. In the majority of mammalian cells, NF-B exists as an inactive form in the cytoplasm by an association with a member of the family of inhibitory molecules (IB), IB-, IB-ß or IB- (1). NF-B is activated by a variety of signals, including cytokines such as tumor necrosis factor (TNF)- and IL-1, bacterial products such as lipopolysaccharide (LPS), oxidative stress, viruses, and DNA-damaging agents. The activation of NF-B complexes is achieved through the degradation of IB and subsequent dissociation of the NF-B–IB complexes (2–6). In the case of IB-, the N-terminal serine residues, Ser32 and Ser36, are phosphorylated in response to signals, followed by polyubiquitination and degradation (7–9). The released NF-B complexes then translocate to the nucleus, where they up-regulate expression of many genes involved in the immune and inflammatory responses.

Recently, two closely related IB kinases (IKKs) have been identified and cloned (10–14). One of the kinases is identical to a previously cloned serine/threonine kinase of unknown function, named CHUK. The structural characteristic of CHUK is that it contains helix-loop-helix and leucine zipper sequences as is often seen in transcriptional factors. The second kinase is highly related to CHUK. CHUK and its relative are now referred to as IKK- and IKK-ß respectively. IKK- and IKK-ß are 52% identical in amino acids. Both kinases directly phosphorylate Ser32 and Ser36 of IB-, and overexpression of each wild-type kinase leads to NF-B activation. The activity of IKK- and IKK-ß is stimulated by TNF- and IL-1 treatment. IKK- and IKK-ß form a heterodimer that can interact directly with the upstream kinase, NIK (12). These three kinases are considered to be present in the large 700 kDa IB kinase complex (15,16).

In an attempt to isolate novel genes that are induced in activated macrophages, and are responsible for immune and inflammatory responses, we prepared a cDNA library from cultures of the LPS-stimulated mouse macrophage cell line, RAW264.7, and screened the library by the suppression subtractive hybridization technique (17). Using this technique, we previously identified a novel LPS-inducible chemokine receptor (18). In addition to this gene, we obtained several clones with a novel sequence. This gene was only slightly expressed in non-stimulated RAW264.7 cells, but was dramatically induced by stimulation with LPS (Fig. 1A). In order to analyze LPS-induced expression of this gene, we stimulated RAW264.7 cells with LPS for various periods and subjected the cells to Northern blot analysis (Fig. 1B). Expression of mRNA for this gene was induced within 2 h after stimulation and reached the peak level at 4 h in RAW264.7 cells. The full-length cDNA of this gene was obtained from the cDNA library of RAW264.7 cells that were activated by LPS for 4 h as described previously (18).

View larger version (42K): [in this window] [in a new window]   Fig. 1. Induction of IKK-i expression by LPS in RAW264.7 cells. (A) RAW264.7 cells were left unstimulated (–) or stimulated (+) with 100 ng/ml LPS (Difco, Detroit, MI) for 4 h. Two micrograms of poly(A)+ RNA was subjected to Northern blot analysis using the IKK-i cDNA fragment obtained from subtraction as probe. The same membrane was rehybridized with G3PDH cDNA probe. (B) RAW264.7 cells were stimulated with 100 ng/ml LPS for the indicated periods. Total RNA was extracted and subjected (25 µg/lane) to Northern blot analysis. The membrane was hybridized with IKK-i cDNA. The same membrane was rehybridized with the G3PDH cDNA probe.

 
The obtained cDNA has an open reading frame of 2151 bp, encoding a protein of 717 amino acids. The deduced amino acid sequence of this cDNA showed 82.3% identity with the human cDNA clone (KIAA0151) of unknown function, indicating that this gene is a murine homologue of KIAA0151. The N-terminal portion of this polypeptide contains a putative serine/threonine kinase domain, whereas the C-terminal portion contains a leucine zipper domain and a potential helix-loop-helix domain (Fig. 2). The catalytic domain of this LPS-inducible protein kinase has a significant similarity (30% identical) with that of IKK-ß, a recently identified serine/threonine kinase that contains a catalytic domain in its N-terminus, and a leucine zipper domain and a helix-loop-helix-domain in its C-terminus (Fig. 2). Thus, this LPS-inducible kinase has a striking structural similarity with a member of the IKK family. Based on its similarity and the novel function of this kinase that we are going to describe in this paper, we designated this kinase IKK-i (for inducible IB kinase).

View larger version (80K): [in this window] [in a new window]   Fig. 2. Amino acid sequence of IKK-i. Alignment of the amino acid sequences of human IKK-i with IKK- and IKK-ß. The solid backgrounds indicate identical amino acid residues. Brackets delineate the boundaries of the kinase domain. The activation loop is boxed. Amino acid residues mutated for some experiments in this paper are asterisked. Two helices of the potential helix-loop-helix domain of IKK-i are overlined, and two helices of the helix-loop-helix domain of IKK- and IKK-ß are underlined. The heptad repeats of hydrophobic residues within the leucine zipper domain of IKK-i are indicated with + on top of the letters and of IKK- and IKK-ß under the letters. The nucleotide and amino acid sequence data reported in this paper are available from DDBJ, EMBL and GenBank under accession numbers AB016590 (human IKK-i) and AB016589 (mouse IKK-i).

 
We examined the tissue distribution of IKK-i transcripts by Northern blot analysis in various human tissues (Fig. 3A). The major IKK-i transcript was 4.0 kb in length. High expression of IKK-i mRNA was observed in thymus, spleen, peripheral blood leukocytes, pancreas and placenta, with the highest expression in spleen. Low expression was observed in lung, kidney, prostate, ovary and colon. We examined LPS-induced expression of IKK-i mRNA in various murine cell lines (Fig. 3B). IKK-i mRNA expression was induced by LPS stimulation in the NK cell line (5E3) and monocytic leukemia cell line (M1). A mouse pre-B cell line (70Z3) and mature B cell line (WEHI231) also showed an increase in IKK-i mRNA in response to LPS. We next examined whether other stimuli induce IKK-i expression. Stimulation of RAW264.7 cells with IL-6 and IFN- induced IKK-i mRNA expression (data not shown). IKK-i mRNA expression was up-regulated upon stimulation of thioglycollate-elicited peritoneal macrophages with TNF-, IL-1ß, IFN- and IL-6 in addition to LPS (Fig. 3C). In contrast, mRNA expression levels of IKK- or IKK-ß were not augmented in response to these stimuli.

View larger version (67K): [in this window] [in a new window]   Fig. 3. Expression of IKK-i mRNA in various tissues. (A) A filter containing 2 µg of poly(A)+ RNAs from various human tissues was hybridized with human IKK-i cDNA probe (Clontech, Palo Alto, CA). PBL; peripheral blood leukocytes. (B) Various murine cell lines were left unstimulated or stimulated with 100 ng/ml LPS (100 µg/ml for 70Z3 and WEHI231) for 4 h. Total RNA was extracted and subjected to Northern blot analysis for IKK-i expression (upper panel). The same membrane was rehybridized with G3PDH cDNA probe (lower panel). (C) C57BL/6 mice were i.p. injected with 2 ml of 4% thioglycollate. Three days later, peritoneal exudate cells were isolated and cultured for 2 h. Adherent cell monolayers were used as peritoneal macrophages. Then, the peritoneal macrophages were stimulated with 250 U/ml IFN- (Genzyme, Cambridge, MA), 100 ng /ml TNF- (Genzyme), 1000 U/ml IL-6 (Genzyme) or 100 ng /ml IL-1ß (Genzyme) for 4 h. Total RNA was extracted, and analyzed for expression of IKK-i, IKK-, IKK-ß and G3PDH by Northern blot. Probes for IKK- and IKK-ß were generated by PCR from a mouse peritoneal exudate cell cDNA library. (D) T or B cells were purified from splenocytes of C57BL/6 mice by magnetic cell sorting (MACS; Miltenyi Biotec, Bergish Gladbach, Germany) using microbeads–Thy-1 or microbeads–B220 respectively. Purified T and B cells were >98% positive for CD3 and B220 as determined by flow cytometry (FACSCalibur; Becton Dickinson, San Jose, CA). The purified B cells were stimulated with 100 mg/ml LPS. Total RNA was extracted and expression of IKK-i was analyzed by Northern blot (upper panel). The same membrane was rehybridized with the G3PDH cDNA probe (lower panel). T, T cell; B, B cell.

 
As described above, IKK-i mRNA is constitutively expressed in spleen. We next examined which cell population expresses IKK-i mRNA in spleen. T and B cell populations were prepared from splenocytes and IKK-i expression was analyzed by Northern blot analysis (Fig. 3D). The T cell population, but not B cell population, expressed IKK-i mRNA constitutively. In the case of B cells, IKK-i expression was induced in response to LPS.

Taken together, IKK-i is predominantly expressed in immune cells and is inducible in response to LPS or other inflammatory cytokines.

We next investigated whether IKK-i phosphorylates IB- in vitro. To express IKK-i in mammalian cells, an N-terminal FLAG epitope-tagged wild-type IKK-i (FLAG-IKK-i WT) was cassetted into the pEF-BOS mammalian expression vector. Human embryonic kidney 293 cells were transiently transfected with FLAG-IKK-i WT. The cells were lysed and immunoprecipitated with anti-FLAG mAb. The kinase activity in the immunoprecipitates was measured by in vitro kinase assay with GST–IB- (residues 1–72) fusion protein or GST–IB- (1–72) mutant with substitution of Ser32 and/or Ser36 to alanine (S32A, S36A and S32,36A) as the substrates. As shown in Fig. 4(A), IKK-i phosphorylated GST-IB- WT and S32A but not GST-IB- S32,36A. S36A was weakly phosphorylated by IKK-i, suggesting that IKK-i phosphorylated preferentially Ser36 of two serine residues, which are important for degradation of IB- and NF-B activation.

View larger version (50K): [in this window] [in a new window]   Fig. 4. IKK-i phosphorylates IB- in vitro and activates NF-B. (A) Human 293 cells were transiently transfected with 10 µg of FLAG-tagged IKK-i WT by lipofection (Qiagen, Hilden, Germany). Thirty-six hours after transfection, cell lysates were immunoprecipitated with anti-FLAG mAb (Sigma, St Louis, MO). The in vitro kinase assay was carried out in the presence of 1.0 µg of GST–IB- WT, S32A, S36A or S32,36A. Proteins were dissolved by SDS–PAGE and visualized by autoradiography. Phosphorylation of GST–IB proteins were indicated (upper panel). The lower panel shows Coomassie blue (CB) staining of the gel. The GST–IB- fusion protein was expressed in Escherichia coli BL-21 in the presence of 0.1 mM isopropyl-1-thio-ß-D-galactopyranoside and purified with glutathione–Sepharose beads (Amersham Pharmacia, Uppsala, Sweden). (B) Human 293 cells were transiently transfected with 10 µg of FLAG-IKK-i WT, K38A, E168A, S172A, S172E or C. After 36 h, the cell lysates were immunoprecipitated with anti-FLAG mAb and the in vitro kinase reaction was carried out in the presence of GST–IB- (1–72) (upper panel). The lower panel shows Western blot analysis of the same lysates with anti-FLAG mAb (Sigma). (C) Effect of overexpression of IKK-i on NF-B-dependent reporter gene activity. Human 293 cells were transiently co-transfected with 1.0 µg of reporter plasmid (pNF-B Luc) (Stratagene, La Jolla, CA) together with the indicated amounts of the expression plasmid for FLAG-IKK-i WT or K38A by lipofection. The total DNA dose was kept constant to 4 µg by supplementation with empty vector (pEF-BOS). Twenty-four hours after transfection, relative luciferase activity was determined and normalized on the basis of sea-pansy luciferase activity (pRL-SV40) (Promega, Madison, WI). Similar results were obtained from five independent experiments in which each transfection was performed in duplicate. (D) 293 and COS-7 cells were transiently transfected with FLAG-IKK-i. Thirty-six hours after transfection, 293 cells (left panels) and COS-7 cells (right panels) were left untreated (–) or treated with 40 ng/ml of TNF- or 40 ng/ml of IL-1ß respectively. Cell lysates were immunoprecipitated with anti-FLAG mAb and the in vitro kinase reaction was carried out in the presence of GST–IB- (1–72) (upper panels). The same lysates were examined by Western blot analysis with anti-phosphorylated p38 MAP kinase (p-p38) (New England Biolabs, Beverly, MA) for TNF- and anti-p-ERK-1 (New England Biolabs) for IL-1 (lower panels). KA, kinase activity; WB, Western blot.

 
We prepared a series of mutant IKK-i to investigate the regulation of the kinase activity of IKK-i. The K38A mutant carries a point mutation in which the lysine residue at 38 is substituted by alanine. The substitution of this residue is known to block the phosphotransfer reaction and results in a kinase-negative mutant in a number of protein kinases, including IKK- and IKK-ß. Phosphorylation of the serine residue at 176, which is present in the activation loop between kinase subdomains VII and VIII, is essential for activation of IKK- (19). Mutation studies indicated that the changes of Ser177 and Ser181 of IKK-ß by alanines decreased its activity, whereas the changes by glutamates enhanced it. Unlike for IKK- and IKK-ß, the residue of IKK-i that corresponds to Ser176 of IKK- is glutamate. Therefore, we prepared three mutants in which the corresponding residues were changed to alanine or glutamate (E168A, S172A and S172E). In addition, a deletion mutant lacking the C-terminal region (C, encoding amino acids 1–543) was also constructed. As shown in Fig. 4(B), both auto- and IB--phosphorylations were completely abolished by the mutation in K38A. The kinase activity of E168A was only slightly decreased compared to that of wild-type. In contrast, the mutation of Ser172 to alanine resulted in the loss of kinase activity. Contrary to our expectation, change of Ser172 to glutamate did not enhance the kinase activity of IKK-i, but rather lost it. Phosphorylation of IB- was not detected in the C mutant, although autophosphorylation was similar to that of wild-type. These results suggest that Ser172 of IKK-i is a major autophosphorylation site and that the C-terminal region is necessary for phosphorylating IB-.

The ability of IKK-i to phosphorylate IB- allowed us to test whether IKK-i induces NF-B activation. Human 293 cells were transiently co-transfected with the indicated amounts of FLAG-IKK-i WT or K38A mutant along with the NF-B-dependent luciferase reporter gene plasmid and luciferase activity was measured. As shown in Fig. 4(C), the luciferase activity was significantly increased by expression of IKK-i WT in a dose-dependent manner. On the other hand, NF-B activation was not altered in K38A mutant-transfected cells. These results indicate that IKK-i mediates NF-B activation through phosphorylation of the N-terminal regulatory region of IB-.

The kinase activity of IKK- and IKK-ß is stimulated by TNF- or IL-1 treatment (10–14). To determine whether the kinase activity of IKK-i is also enhanced by these cytokines, we transiently transfected FLAG-tagged IKK-i in 293 cells or COS-7 cells. Thirty-six hours later, 293 cells were treated with TNF- and COS-7 cells were treated with IL-1ß for 3 or 7 min (Fig. 4D). Then cells were lysed and anti-FLAG immunoprecipitates were examined by an in vitro kinase assay. To prove that the cells were stimulated by these cytokines, Western blot analysis was performed for the cell lysate of TNF--treated 293 cells with anti-phosphorylated p38 MAP kinase (p-p38) antibody, and for the cell lysate of IL-1-treated COS-7 cells with anti-phosphorylated extracellular signal-regulated kinase (p-ERK)-1 antibody. p-p38 and p-ERK-1 increased by treating the cells with these cytokines, but both TNF- and IL-1 did not change the degree of phosphorylation of exogenous IB-, indicating that the kinase activity of IKK-i is not enhanced by these cytokines.

In the present study, we describe the cloning and initial characterization of a novel IB kinase that shows homology with IKK- and IKK-ß. NF-B activation depends on the signal-induced phosphorylation of IB proteins at two specific serine residues: Ser32 and Ser36 in the case of IB-, and Ser19 and Ser23 in IB-ß (20). The proteosome-dependent destruction of IB requires dual phosphorylation of the serine residues. Although IKK-i primarily phosphorylates the second serine residue of IB-, transient overexpression of IKK-i is able to significantly stimulate NF-B activation, suggesting that the phosphorylation of the second serine residue may be sufficient for the ubiquitination and destruction of IB-. In fact, the IKK complex is shown to have some preference for the second serine residue as compared with the first one of IB proteins (20). Alternatively, the dual phosphorylation of IB proteins may be mediated by the combined action of phosphorylation of the second serine residue by IKK-i and phosphorylation of the first serine residue by other kinases such as mitogen-activated 90 kDa ribosomal S6 kinase and casein kinase II (20,21).

The kinase activities of IKK- and IKK-ß are augmented in response to TNF- and IL-1 stimulation (10,11,13,14), and are regulated by two upstream kinases, NIK and MEKK1 of the MAP3K family (12,19,22,23). MAP3K is shown to activate MAP2K by phosphorylating serine and threonine residues in the activation loop between kinase subdomain VII and VIII (24). Both IKK- and IKK-ß contain a canonical MAP2K activation loop motif (Ser-X-X-X-Ser, where X is any amino acid) (11). In addition to the position of the serine residues, the surrounding amino acid sequence is also conserved between IKK- and IKK-ß. It has been demonstrated that phosphorylation of IKK- by NIK occurs specifically on Ser176 (19). The phosphorylation of IB- by IKK- was greatly impaired when Ser176 of IKK- was mutated to alanine. In contrast, mutation of Ser176 to glutamate significantly enhanced the IKK- activity (19). Similarly, mutation of two corresponding serine residues of IKK-ß to alanine residues abolished the kinase activity, while mutation to glutamate residues enhanced it (11). In the case of IKK-i, the corresponding region is not conserved and the amino acid corresponding to Ser176 of IKK- is replaced by glutamate. Mutation of the Ser172 to alanine abolished the autophosphorylation of IKK-i as well as IB- phosphorylation. The replacement of the critical serine residue of IKK-i with glutamate did not augment IB- kinase activity, but rather decreased it. Neither NIK nor MEKK1 phosphorylated IKK-i and co-transfection with NIK or MEKK1 did not augment IKK-i kinase activity (our unpublished data). Immunoprecipitation experiments showed that IKK-i did not associate with either IKK- or IKK-ß, indicating that IKK-i may not be involved in the formation of the 700 kDa IKK complex (our unpublished data).

Taken together, these results suggest that phosphorylation of Ser172 of IKK-i is essential for autophosphorylation and IB kinase activity, but is not augmented by the upstream kinases, NIK and MEKK1. This may be also consistent with the fact that IKK-i autophosphorylation and IB kinase activity is not augmented in response to either IL-1 or TNF-. The fact that overexpression of IKK-i is enough for autophosphorylation as well as NF-B activation suggests that IKK-i activity may be mainly regulated at the level of mRNA induction, but not at the level of phosphorylation by stimuli-activated kinases. At present, the kinase that phosphorylates serine residues of IKK-i remains unknown. IKK-i, itself, may autophosphorylate Ser172.

Finally, although T cells express IKK-i mRNA constitutively, we could not detect NF-B activation in T cells (our unpublished data), just that IKK-i mRNA induction is not sufficient for NF-B activation. There may be translational regulation of IKK-i mRNA or an inhibitor(s) present in T cells. Further work including expression of IKK-i protein and generation of IKK-i-deficient mice will reveal the role of IKK-i in the immune and inflammatory responses.

	Acknowledgments

 
We thank K. Nakanishi and T. Kaisho for providing several cell lines, and T. Aoki and M. Hyuga for excellent secretarial assistance. This work was supported by grants from the Ministry of Education of Japan.

	Abbreviations

 

IKK	IB kinase
LPS	lipopolysaccharide
p-ERK	phosphorylated extracellular signal-regulated kinase
TNF	tumor necrosis factor

	Notes

 
Transmitting editor: S. Nishikawa

⁵ Present address: Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan

Received 7 April 1999, accepted 16 April 1999.

	References

Top Abstract Introduction References

 

1. Ghosh, S., May, M. J. and Kopp, E. B. 1998. NF-B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16:225.[Web of Science][Medline]
2. Baeuerle, P. A. and Henkel, T. 1994. Function and activation of NF-B in immune system. Annu. Rev. Immunol. 12:141.[Web of Science][Medline]
3. Verma, I. M., Stevenson, J. K., Schwarz, E. M., van Antwerp, D. and Miyamoto, S. 1995. Rel/NF-B/IB family: intimate tales of association and dissociation. Genes Dev. 9:2723.[Free Full Text]
4. Thanos, D. and Maniatis, T. 1995. NF-B: a lesson in family values. Cell 80:529.[Web of Science][Medline]
5. Baeuerle, P. A. and Baltimore, D. 1996. NF-B: ten years after. Cell 87:13.[Web of Science][Medline]
6. May, M. J. and Ghosh, S. 1998. Signal transduction through NF-kappa B. Immunol. Today 19:80.[Web of Science][Medline]
7. Chen, Z., Hagler, J., Palombella, V. J., Melandri, F., Schere, D., Ballard, D. and Maniatis, T. 1995. Signal-induced site-specific phosphorylation targets IB to the ubiquitin–proteasome pathway. Genes Dev. 9:1586.[Abstract/Free Full Text]
8. Traenckner, E. B., Pahl, H. L., Henkel, T., Schmidt, K. N., Wilk, S. and Baeuerle, P. A. 1995. Phosphorylation of human I kappa B-alpha on serines 32 and 36 controls I kappa B-alpha proteolysis and NF-kappa B activation in response to diverse stimuli. EMBO J. 14:2876.[Web of Science][Medline]
9. DiDonato, J. A., Mercurio, F., Rosette, C., Wu-Ii, J., Suyang, H., Ghosh, S. and Karin, M. 1996. Mapping of the inducible IB phosphorylation sites that signal its ubiquitination and degradation. Mol. Cell. Biol. 16:1295.[Abstract]
10. DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E. and Karin, M. 1997. A cytokine-responsive IB kinase that activates the transcription factor NF-B. Nature 388:548.[Medline]
11. Mercurio, F., Zhu, H., Murray, B. W., Shevchenko, A., Bennett, B. L., Li, J. W., Young, D. B., Barbosa, M., Mann, M., Manning, A. and Rao, A. 1997. IKK-1 and IKK-2: cytokine-activated IB kinases essential for NF-B activation. Science 278:860.[Abstract/Free Full Text]
12. Regnier C. H., Song, H. Y., Gao, X., Goeddel, D. V., Cao, Z. and Rothe, M. 1997. Identification and characterization of an IB kinase. Cell 90:373.[Web of Science][Medline]
13. Woronicz, J. D., Gao, X., Cao, Z., Rothe, M. and Goeddel, D. V. 1997. IB kinase-ß: NF-B activation and complex formation with IB kinase-ß and NIK. Science 278:866.[Abstract/Free Full Text]
14. Zandi, E., Rothwarf, D. M., Delhase, M., Hayakawa, M. and Karin, M. 1997. The IB kinase complex (IKK) contains two kinase subunits, IKK and IKKß, necessary for IB phosphorylation and NF-B activation. Cell 91:243.[Web of Science][Medline]
15. Chen, Z. J., Parent, L. and Maniatis, T. 1996. Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity. Cell 84:853.[Web of Science][Medline]
16. Cohen, L., Henzel, W. J. and Baeuerle, P. A. 1998. IKAP is a scaffold protein of the IkappaB kinase complex. Nature 395:292.[Medline]
17. Diatchenko, L., Lau, Y. F., Campbell, A. P., Chenchik, A., Moqadam, F., Huang, B., Lukyanov, S., Lukyanov,K., Gurskaya, N., Sverdlov, E. D. and Siebert, P. D. 1996. Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc. Natl Acad. Sci. USA 93:6025.[Abstract/Free Full Text]
18. Shimada, T., Matsumoto, M., Tatsumi, Y., Kanamaru, A. and Akira, S. 1998. A novel lipopolysaccharide inducible C–C chemokine receptor related gene in murine macrophages. FEBS Lett. 425:490.[Web of Science][Medline]
19. Ling, L., Cao, Z. and Goeddel D. V. 1998. NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser176. Proc. Natl Acad. Sci. USA 95:3792.[Abstract/Free Full Text]
20. Heilker, R., Freuler, F., Pulfer, R., Di Padova, F. and Eder J. 1999. All three IB isoforms and most Rel family members are stably associated with the IB kinase 1/2 complex. Eur. J. Biochem. 259:253.[Web of Science][Medline]
21. Schouten, G. J., Vertegaal, A. C. O., Whiteside, S. T., Israel, A., Toebes, M., Dorsman, J. C., van der Eb, A. J. and Zantema, A. 1997. IB is a target for the mitogen-activated 90 kDa ribosomal S6 kinase. EMBO J. 16:3133.[Web of Science][Medline]
22. Karin, M. and Delhase, M. 1998. JNK or IKK, AP-1 or NF-kappaB, which are the targets for MEK kinase 1 action? Proc. Natl Acad. Sci. USA 95:9067.[Free Full Text]
23. Lee, F. S., Peters, R. T., Dang, L. C. and Maniatis, T. 1998. MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta. Proc. Natl Acad. Sci. USA 95:9319.[Abstract/Free Full Text]
24. Zheng, C. F. and Guan, K. L. 1994. Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. EMBO J. 13:1123.[Web of Science][Medline]

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				J.-P. Guo, S.-K. Shu, L. He, Y.-C. Lee, P. A. Kruk, S. Grenman, S. V. Nicosia, G. Mor, M. J. Schell, D. Coppola, et al. Deregulation of IKBKE Is Associated with Tumor Progression, Poor Prognosis, and Cisplatin Resistance in Ovarian Cancer Am. J. Pathol., July 1, 2009; 175(1): 324 - 333. [Abstract] [Full Text] [PDF]

				S. Paz, M. Vilasco, M. Arguello, Q. Sun, J. Lacoste, T. L.-A. Nguyen, T. Zhao, E. A. Shestakova, S. Zaari, A. Bibeau-Poirier, et al. Ubiquitin-Regulated Recruitment of I{kappa}B Kinase {varepsilon} to the MAVS Interferon Signaling Adapter Mol. Cell. Biol., June 15, 2009; 29(12): 3401 - 3412. [Abstract] [Full Text] [PDF]

				K. Clark, L. Plater, M. Peggie, and P. Cohen Use of the Pharmacological Inhibitor BX795 to Study the Regulation and Physiological Roles of TBK1 and I{kappa}B Kinase {epsilon}: A DISTINCT UPSTREAM KINASE MEDIATES SER-172 PHOSPHORYLATION AND ACTIVATION J. Biol. Chem., May 22, 2009; 284(21): 14136 - 14146. [Abstract] [Full Text] [PDF]

				K. C. Prins, W. B. Cardenas, and C. F. Basler Ebola Virus Protein VP35 Impairs the Function of Interferon Regulatory Factor-Activating Kinases IKK{varepsilon} and TBK-1 J. Virol., April 1, 2009; 83(7): 3069 - 3077. [Abstract] [Full Text] [PDF]

				M. J Vervoordeldonk, C. J Aalbers, and P. P Tak Interferon {beta} for rheumatoid arthritis: new clothes for an old kid on the block Ann Rheum Dis, February 1, 2009; 68(2): 157 - 158. [Full Text] [PDF]

				D. Verpooten, Y. Ma, S. Hou, Z. Yan, and B. He Control of TANK-binding Kinase 1-mediated Signaling by the {gamma}134.5 Protein of Herpes Simplex Virus 1 J. Biol. Chem., January 9, 2009; 284(2): 1097 - 1105. [Abstract] [Full Text] [PDF]

				E. Niederberger and G. Geisslinger The IKK-NF-{kappa}B pathway: a source for novel molecular drug targets in pain therapy? FASEB J, October 1, 2008; 22(10): 3432 - 3442. [Abstract] [Full Text] [PDF]

				D.-F. Lee and M.-C. Hung Advances in Targeting IKK and IKK-Related Kinases for Cancer Therapy Clin. Cancer Res., September 15, 2008; 14(18): 5656 - 5662. [Abstract] [Full Text] [PDF]

				M. Zhang, X. Wu, A. J. Lee, W. Jin, M. Chang, A. Wright, T. Imaizumi, and S.-C. Sun Regulation of I{kappa}B Kinase-related Kinases and Antiviral Responses by Tumor Suppressor CYLD J. Biol. Chem., July 4, 2008; 283(27): 18621 - 18626. [Abstract] [Full Text] [PDF]

				J.-F. Clement, A. Bibeau-Poirier, S.-P. Gravel, N. Grandvaux, E. Bonneil, P. Thibault, S. Meloche, and M. J. Servant Phosphorylation of IRF-3 on Ser 339 Generates a Hyperactive Form of IRF-3 through Regulation of Dimerization and CBP Association J. Virol., April 15, 2008; 82(8): 3984 - 3996. [Abstract] [Full Text] [PDF]

				B. R. tenOever, S.-L. Ng, M. A. Chua, S. M. McWhirter, A. Garcia-Sastre, and T. Maniatis Multiple Functions of the IKK-Related Kinase IKK{epsilon} in Interferon-Mediated Antiviral Immunity Science, March 2, 2007; 315(5816): 1274 - 1278. [Abstract] [Full Text] [PDF]

				B. Peant, J.-S. Diallo, L. Lessard, N. Delvoye, C. Le Page, F. Saad, and A.-M. Mes-Masson Regulation of I{kappa}B Kinase {varepsilon} Expression by the Androgen Receptor and the Nuclear Factor-{kappa}B Transcription Factor in Prostate Cancer Mol. Cancer Res., January 1, 2007; 5(1): 87 - 94. [Abstract] [Full Text] [PDF]

				C. Wietek, C. S. Cleaver, V. Ludbrook, J. Wilde, J. White, D. J. Bell, M. Lee, M. Dickson, K. P. Ray, and L. A. J. O'Neill I{kappa}B Kinase {epsilon} Interacts with p52 and Promotes Transactivation via p65 J. Biol. Chem., November 17, 2006; 281(46): 34973 - 34981. [Abstract] [Full Text] [PDF]

				H. Hacker and M. Karin Regulation and Function of IKK and IKK-Related Kinases Sci. Signal., October 17, 2006; 2006(357): re13 - re13. [Abstract] [Full Text] [PDF]

				A. Bibeau-Poirier, S.-P. Gravel, J.-F. Clement, S. Rolland, G. Rodier, P. Coulombe, J. Hiscott, N. Grandvaux, S. Meloche, and M. J. Servant Involvement of the I{kappa}B Kinase (IKK)-Related Kinases Tank-Binding Kinase 1/IKKi and Cullin-Based Ubiquitin Ligases in IFN Regulatory Factor-3 Degradation J. Immunol., October 15, 2006; 177(8): 5059 - 5067. [Abstract] [Full Text] [PDF]

				M. Adli and A. S. Baldwin IKK-i/IKK{epsilon} Controls Constitutive, Cancer Cell-associated NF-{kappa}B Activity via Regulation of Ser-536 p65/RelA Phosphorylation J. Biol. Chem., September 15, 2006; 281(37): 26976 - 26984. [Abstract] [Full Text] [PDF]

				J. Harris, S. Oliere, S. Sharma, Q. Sun, R. Lin, J. Hiscott, and N. Grandvaux Nuclear Accumulation of cRel following C-Terminal phosphorylation by TBK1/IKK{epsilon} J. Immunol., August 15, 2006; 177(4): 2527 - 2535. [Abstract] [Full Text] [PDF]

				L. Pei, A. Castrillo, and P. Tontonoz Regulation of Macrophage Inflammatory Gene Expression by the Orphan Nuclear Receptor Nur77 Mol. Endocrinol., April 1, 2006; 20(4): 786 - 794. [Abstract] [Full Text] [PDF]

				I. Mattioli, H. Geng, A. Sebald, M. Hodel, C. Bucher, M. Kracht, and M. L. Schmitz Inducible Phosphorylation of NF-{kappa}B p65 at Serine 468 by T Cell Costimulation Is Mediated by IKK{epsilon} J. Biol. Chem., March 10, 2006; 281(10): 6175 - 6183. [Abstract] [Full Text] [PDF]

				S. F. Eddy, S. Guo, E. G. Demicco, R. Romieu-Mourez, E. Landesman-Bollag, D. C. Seldin, and G. E. Sonenshein Inducible I{kappa}B Kinase/I{kappa}B Kinase {varepsilon} Expression Is Induced by CK2 and Promotes Aberrant Nuclear Factor-{kappa}B Activation in Breast Cancer Cells Cancer Res., December 15, 2005; 65(24): 11375 - 11383. [Abstract] [Full Text] [PDF]

				T. Ear, A. Cloutier, and P. P. McDonald Constitutive Nuclear Expression of the I{kappa}B Kinase Complex and Its Activation in Human Neutrophils J. Immunol., August 1, 2005; 175(3): 1834 - 1842. [Abstract] [Full Text] [PDF]

				M. L. Shaw, W. B. Cardenas, D. Zamarin, P. Palese, and C. F. Basler Nuclear Localization of the Nipah Virus W Protein Allows for Inhibition of both Virus- and Toll-Like Receptor 3-Triggered Signaling Pathways J. Virol., May 15, 2005; 79(10): 6078 - 6088. [Abstract] [Full Text] [PDF]

				S. E. Sweeney, D. Hammaker, D. L. Boyle, and G. S. Firestein Regulation of c-Jun Phosphorylation by the I{kappa}B Kinase-{epsilon} Complex in Fibroblast-Like Synoviocytes J. Immunol., May 15, 2005; 174(10): 6424 - 6430. [Abstract] [Full Text] [PDF]

				A. Caillaud, A. G. Hovanessian, D. E. Levy, and I. J. Marie Regulatory Serine Residues Mediate Phosphorylation-dependent and Phosphorylation-independent Activation of Interferon Regulatory Factor 7 J. Biol. Chem., May 6, 2005; 280(18): 17671 - 17677. [Abstract] [Full Text] [PDF]

				A. Schoenemeyer, B. J. Barnes, Margo. E. Mancl, E. Latz, N. Goutagny, P. M. Pitha, K. A. Fitzgerald, and D. T. Golenbock The Interferon Regulatory Factor, IRF5, Is a Central Mediator of Toll-like Receptor 7 Signaling J. Biol. Chem., April 29, 2005; 280(17): 17005 - 17012. [Abstract] [Full Text] [PDF]

				A. Breiman, N. Grandvaux, R. Lin, C. Ottone, S. Akira, M. Yoneyama, T. Fujita, J. Hiscott, and E. F. Meurs Inhibition of RIG-I-Dependent Signaling to the Interferon Pathway during Hepatitis C Virus Expression and Restoration of Signaling by IKK{varepsilon} J. Virol., April 1, 2005; 79(7): 3969 - 3978. [Abstract] [Full Text] [PDF]

				S.-P. Gravel and M. J. Servant Roles of an I{kappa}B Kinase-related Pathway in Human Cytomegalovirus-infected Vascular Smooth Muscle Cells: A MOLECULAR LINK IN PATHOGEN-INDUCED PROATHEROSCLEROTIC CONDITIONS J. Biol. Chem., March 4, 2005; 280(9): 7477 - 7486. [Abstract] [Full Text] [PDF]

				K. Takeda Evolution and integration of innate immune recognition systems: the Toll-like receptors Innate Immunity, February 1, 2005; 11(1): 51 - 55. [Abstract] [PDF]

				B. R. tenOever, S. Sharma, W. Zou, Q. Sun, N. Grandvaux, I. Julkunen, H. Hemmi, M. Yamamoto, S. Akira, W.-C. Yeh, et al. Activation of TBK1 and IKK{varepsilon} Kinases by Vesicular Stomatitis Virus Infection and the Role of Viral Ribonucleoprotein in the Development of Interferon Antiviral Immunity J. Virol., October 1, 2004; 78(19): 10636 - 10649. [Abstract] [Full Text] [PDF]

				H. Hemmi, O. Takeuchi, S. Sato, M. Yamamoto, T. Kaisho, H. Sanjo, T. Kawai, K. Hoshino, K. Takeda, and S. Akira The Roles of Two I{kappa}B Kinase-related Kinases in Lipopolysaccharide and Double Stranded RNA Signaling and Viral Infection J. Exp. Med., June 21, 2004; 199(12): 1641 - 1650. [Abstract] [Full Text] [PDF]

				A. K. Perry, E. K. Chow, J. B. Goodnough, W.-C. Yeh, and G. Cheng Differential Requirement for TANK-binding Kinase-1 in Type I Interferon Responses to Toll-like Receptor Activation and Viral Infection J. Exp. Med., June 21, 2004; 199(12): 1651 - 1658. [Abstract] [Full Text] [PDF]

				C. Monaco and E. Paleolog Nuclear factor {kappa}B: a potential therapeutic target in atherosclerosis and thrombosis Cardiovasc Res, March 1, 2004; 61(4): 671 - 682. [Abstract] [Full Text] [PDF]

				S. M. McWhirter, K. A. Fitzgerald, J. Rosains, D. C. Rowe, D. T. Golenbock, and T. Maniatis From The Cover: IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts PNAS, January 6, 2004; 101(1): 233 - 238. [Abstract] [Full Text] [PDF]

				F. Fujita, Y. Taniguchi, T. Kato, Y. Narita, A. Furuya, T. Ogawa, H. Sakurai, T. Joh, M. Itoh, M. Delhase, et al. Identification of NAP1, a Regulatory Subunit of I{kappa}B Kinase-Related Kinases That Potentiates NF-{kappa}B Signaling Mol. Cell. Biol., November 1, 2003; 23(21): 7780 - 7793. [Abstract] [Full Text] [PDF]

				D Hammaker, S Sweeney, and G S Firestein Signal transduction networks in rheumatoid arthritis Ann Rheum Dis, November 1, 2003; 62(90002): ii86 - 89. [Abstract] [Full Text] [PDF]

				S. Sato, M. Sugiyama, M. Yamamoto, Y. Watanabe, T. Kawai, K. Takeda, and S. Akira Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-{beta} (TRIF) Associates with TNF Receptor-Associated Factor 6 and TANK-Binding Kinase 1, and Activates Two Distinct Transcription Factors, NF-{kappa}B and IFN-Regulatory Factor-3, in the Toll-Like Receptor Signaling J. Immunol., October 15, 2003; 171(8): 4304 - 4310. [Abstract] [Full Text] [PDF]

				K. A. Fitzgerald, D. C. Rowe, B. J. Barnes, D. R. Caffrey, A. Visintin, E. Latz, B. Monks, P. M. Pitha, and D. T. Golenbock LPS-TLR4 Signaling to IRF-3/7 and NF-{kappa}B Involves the Toll Adapters TRAM and TRIF J. Exp. Med., October 6, 2003; 198(7): 1043 - 1055. [Abstract] [Full Text] [PDF]

				M. Yamamoto, S. Sato, H. Hemmi, K. Hoshino, T. Kaisho, H. Sanjo, O. Takeuchi, M. Sugiyama, M. Okabe, K. Takeda, et al. Role of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling Pathway Science, August 1, 2003; 301(5633): 640 - 643. [Abstract] [Full Text] [PDF]

				V. V. Kravchenko, J. C. Mathison, K. Schwamborn, F. Mercurio, and R. J. Ulevitch IKKi/IKK{epsilon} Plays a Key Role in Integrating Signals Induced by Pro-inflammatory Stimuli J. Biol. Chem., July 11, 2003; 278(29): 26612 - 26619. [Abstract] [Full Text] [PDF]

				J. C. Reed, K. Doctor, A. Rojas, J. M. Zapata, C. Stehlik, L. Fiorentino, J. Damiano, W. Roth, S.-i. Matsuzawa, R. Newman, et al. Comparative Analysis of Apoptosis and Inflammation Genes of Mice and Humans Genome Res., June 1, 2003; 13(6): 1376 - 1388. [Abstract] [Full Text] [PDF]

				S. Sharma, B. R. tenOever, N. Grandvaux, G.-P. Zhou, R. Lin, and J. Hiscott Triggering the Interferon Antiviral Response Through an IKK-Related Pathway Science, May 16, 2003; 300(5622): 1148 - 1151. [Abstract] [Full Text] [PDF]

				S. Uematsu, M. Matsumoto, K. Takeda, and S. Akira Lipopolysaccharide-Dependent Prostaglandin E2 Production Is Regulated by the Glutathione-Dependent Prostaglandin E2 Synthase Gene Induced by the Toll-Like Receptor 4/MyD88/NF-IL6 Pathway J. Immunol., June 1, 2002; 168(11): 5811 - 5816. [Abstract] [Full Text] [PDF]

				N. Kishore, Q. K. Huynh, S. Mathialagan, T. Hall, S. Rouw, D. Creely, G. Lange, J. Caroll, B. Reitz, A. Donnelly, et al. IKK-i and TBK-1 are Enzymatically Distinct from the Homologous Enzyme IKK-2. COMPARATIVE ANALYSIS OF RECOMBINANT HUMAN IKK-i, TBK-1, AND IKK-2 J. Biol. Chem., April 12, 2002; 277(16): 13840 - 13847. [Abstract] [Full Text] [PDF]

				Q. K. Huynh, N. Kishore, S. Mathialagan, A. M. Donnelly, and C. S. Tripp Kinetic Mechanisms of Ikappa B-related Kinases (IKK) Inducible IKK and TBK-1 Differ from IKK-1/IKK-2 Heterodimer J. Biol. Chem., April 5, 2002; 277(15): 12550 - 12558. [Abstract] [Full Text] [PDF]

				G. Nelson, L. Paraoan, D. G. Spiller, G. J. C. Wilde, M. A. Browne, P. K. Djali, J. F. Unitt, E. Sullivan, E. Floettmann, and M. R. H. White Multi-parameter analysis of the kinetics of NF-{kappa}B signalling and transcription in single living cells J. Cell Sci., March 15, 2002; 115(6): 1137 - 1148. [Abstract] [Full Text] [PDF]

				S. K. Pandey, H.-J. He, A. Chesley, M. Juhaszova, M. T. Crow, and M. Bernier Wortmannin-Sensitive Pathway Is Required for Insulin-Stimulated Phosphorylation of Inhibitor {kappa}B{alpha} Endocrinology, February 1, 2002; 143(2): 375 - 385. [Abstract] [Full Text] [PDF]

				F. Chen, J. Bower, S. S. Leonard, M. Ding, Y. Lu, Y. Rojanasakul, H.-f. Kung, V. Vallyathan, V. Castranova, and X. Shi Protective Roles of NF-kappa B for Chromium(VI)-induced Cytotoxicity Is Revealed by Expression of Ikappa B Kinase-beta Mutant J. Biol. Chem., January 25, 2002; 277(5): 3342 - 3349. [Abstract] [Full Text] [PDF]

				J. Fan, R. D. Ye, and A. B. Malik Transcriptional mechanisms of acute lung injury Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1037 - L1050. [Abstract] [Full Text] [PDF]

				S. H. Diks, S. J.H. van Deventer, and M. P. Peppelenbosch Invited review: Lipopolysaccharide recognition, internalisation, signalling and other cellular effects Innate Immunity, October 1, 2001; 7(5): 335 - 348. [Abstract] [PDF]

				G. Valen, Z.-q. Yan, and G.o. K. Hansson Nuclear factor kappa-B and the heart J. Am. Coll. Cardiol., August 1, 2001; 38(2): 307 - 314. [Abstract] [Full Text] [PDF]

				N. H. Purcell, C. Yu, D. He, J. Xiang, N. Paran, J. A. DiDonato, S. Yamaoka, Y. Shaul, and A. Lin Activation of NF-{kappa}B by hepatitis B virus X protein through an I{kappa}B kinase-independent mechanism Am J Physiol Gastrointest Liver Physiol, April 1, 2001; 280(4): G669 - G677. [Abstract] [Full Text] [PDF]

				W. Oitzinger, R. Hofer-Warbinek, J. A. Schmid, Y. Koshelnick, B. R. Binder, and R. de Martin Adenovirus-mediated expression of a mutant I{kappa}B kinase 2 inhibits the response of endothelial cells to inflammatory stimuli Blood, March 15, 2001; 97(6): 1611 - 1617. [Abstract] [Full Text] [PDF]

				A. E. King, H. O.D. Critchley, and R. W. Kelly The NF-{{kappa}}B pathway in human endometrium and first trimester decidua Mol. Hum. Reprod., February 1, 2001; 7(2): 175 - 183. [Abstract] [Full Text] [PDF]

				M. Lee and Y. J. Jeon Paclitaxel-Induced Immune Suppression Is Associated with NF-{kappa}B Activation Via Conventional PKC Isotypes in Lipopolysaccharide-Stimulated 70Z/3 Pre-B Lymphocyte Tumor Cells Mol. Pharmacol., February 1, 2001; 59(2): 248 - 253. [Abstract] [Full Text]

				Rainer de Martin, M. Hoeth, R. Hofer-Warbinek, and J. A. Schmid The Transcription Factor NF-{kappa}B and the Regulation of Vascular Cell Function Arterioscler Thromb Vasc Biol, November 1, 2000; 20 (11): e83 - e88. [Abstract] [Full Text] [PDF]

				N. Silverman, R. Zhou, S. Stöven, N. Pandey, D. Hultmark, and T. Maniatis A Drosophila Ikappa B kinase complex required for Relish cleavage and antibacterial immunity Genes & Dev., October 1, 2000; 14(19): 2461 - 2471. [Abstract] [Full Text]

				M. J. May, F. D'Acquisto, L. A. Madge, J. Glöckner, J. S. Pober, and S. Ghosh Selective Inhibition of NF-kappa B Activation by a Peptide That Blocks the Interaction of NEMO with the Ikappa B Kinase Complex Science, September 1, 2000; 289(5484): 1550 - 1554. [Abstract] [Full Text]

				S. K. Manna, N. K. Sah, R. A. Newman, A. Cisneros, and B. B. Aggarwal Oleandrin Suppresses Activation of Nuclear Transcription Factor-{{kappa}}B, Activator Protein-1, and c-Jun NH2-Terminal Kinase Cancer Res., July 1, 2000; 60(14): 3838 - 3847. [Abstract] [Full Text]

				P. Renard, Y. Percherancier, M. Kroll, D. Thomas, J.-L. Virelizier, F. Arenzana-Seisdedos, and F. Bachelerie Inducible NF-kappa B Activation Is Permitted by Simultaneous Degradation of Nuclear Ikappa Balpha J. Biol. Chem., May 12, 2000; 275(20): 15193 - 15199. [Abstract] [Full Text] [PDF]

				Y.-k. Zhang, X. Sun, K.-i. Muraoka, A. Ikeda, S. Miyamoto, H. Shimizu, K. Yoshioka, and K.-i. Yamamoto Immunosuppressant FK506 Activates NF-kappa B through the Proteasome-mediated Degradation of Ikappa Balpha . REQUIREMENT FOR Ikappa Balpha N-TERMINAL PHOSPHORYLATION BUT NOT UBIQUITINATION SITES J. Biol. Chem., December 3, 1999; 274(49): 34657 - 34662. [Abstract] [Full Text] [PDF]

				K. Schwamborn, R. Weil, G. Courtois, S. T. Whiteside, and A. Israel Phorbol Esters and Cytokines Regulate the Expression of the NEMO-related Protein, a Molecule Involved in a NF-kappa B-independent Pathway J. Biol. Chem., July 21, 2000; 275(30): 22780 - 22789. [Abstract] [Full Text] [PDF]

				A. Foryst-Ludwig and M. Naumann p21-activated Kinase 1 Activates the Nuclear Factor kappa B (NF-kappa B)-inducing Kinase-Ikappa B Kinases NF-kappa B Pathway and Proinflammatory Cytokines in Helicobacter pylori Infection J. Biol. Chem., December 8, 2000; 275(50): 39779 - 39785. [Abstract] [Full Text] [PDF]

				N. Inohara, Y. Ogura, F. F. Chen, A. Muto, and G. Nunez Human Nod1 Confers Responsiveness to Bacterial Lipopolysaccharides J. Biol. Chem., January 19, 2001; 276(4): 2551 - 2554. [Abstract] [Full Text] [PDF]

				P. C. Lucas, M. Yonezumi, N. Inohara, L. M. McAllister-Lucas, M. E. Abazeed, F. F. Chen, S. Yamaoka, M. Seto, and G. Nunez Bcl10 and MALT1, Independent Targets of Chromosomal Translocation in MALT Lymphoma, Cooperate in a Novel NF-kappa B Signaling Pathway J. Biol. Chem., May 25, 2001; 276(22): 19012 - 19019. [Abstract] [Full Text] [PDF]

				L. M. McAllister-Lucas, N. Inohara, P. C. Lucas, J. Ruland, A. Benito, Q. Li, S. Chen, F. F. Chen, S. Yamaoka, I. M. Verma, et al. Bimp1, a MAGUK Family Member Linking Protein Kinase C Activation to Bcl10-mediated NF-kappa B Induction J. Biol. Chem., August 10, 2001; 276(33): 30589 - 30597. [Abstract] [Full Text] [PDF]

				K. Hughes, S. Edin, A. Antonsson, and T. Grundstrom Calmodulin-dependent Kinase II Mediates T Cell Receptor/CD3- and Phorbol Ester-induced Activation of Ikappa B Kinase J. Biol. Chem., September 14, 2001; 276(38): 36008 - 36013. [Abstract] [Full Text] [PDF]

This Article Abstract FREE Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (151) Request Permissions Google Scholar Articles by Shimada, T. Articles by Akira, S. Search for Related Content PubMed PubMed Citation Articles by Shimada, T. Articles by Akira, S. Social Bookmarking          What's this?

Online ISSN 1460-2377 - Print ISSN 0953-8178

Copyright © 2009 Japanese Society for Immunology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics