Background
NF-kB (nuclear factor kB) is sequestered in the cytoplasm by IkB family of inhibitory proteins that mask the nuclear localization signal of NF-kB thereby preventing translocation of NF-kB to the nucleus. External stimuli such as tumor necrosis factor or other cytokines results in phosphorylation and degradation of IkB releasing NF-kB dimers. NF-kB dimer subsequently translocates to the nucleus and activates target genes. Synthesis of IkBa is autoregulated. IkB proteins are phosphorylated by IkB kinase complex consisting of at least three proteins, IKK1/a, IKK2/b, and IKK3/g. In vitro, IKK1/a and IKK2/b can form homo- and heterodimers that can phosphorylate IkBs at the regulatory serine residues directly. IKK1/a and IKK2/b are phosphorylated by NF-kB-inducing kinase (NIK) and MAP kinase kinase kinase-1 (MEKK1) (1), respectively. Targeted disruption of IKK1/a gene in mice results in skin and limb abnormalities and death of newborns (2,3).

Antigen
This antibody was raised against a His-tagged full-length human IKKa/IKK1 protein.

Genebank Info (Protein)
NP_001269

Related Products

Reference
1. Delhase, M., Hayakawa, et al. Science 284: 309-313 (1999).
2. Takada, K., et al. Science 284: 313-316 (1999).
3. Hu, Y., Baud, V., Delhase, M., et al. Science 284: 316-320 (1999).

Product Citations
1. Aberrant NF-kB2/p52 expression in Hodgkin/Reed-Sternberg cells and CD30-transformed rat fibroblasts. Mizuho Nonaka, Ryouichi Horie, Kinji Itoh, Toshiki Watanabe, Naoki Yamamoto and Shoji Yamaoka. Oncogene 24, 3976-3986 (2005).
2. The Carboxyl-Terminal Region of IkB Kinase (IKKa) Is Required for Full IKK Activation. Constantin Makris, Jaclyn L. Roberts, and Michael Karin. Mol. Cell. Biol., 22: 6573-6581 (2002).
3. NEMO Trimerizes through Its Coiled-coil C-terminal Domain. Fabrice Agou, Fei Ye, Stéphane Goffinont, Gilles Courtois, Shoji Yamaoka, Alain Israël, and Michel Véron. J. Biol. Chem, 277: 17464–17475 (2002).
4. Methotrexate Suppresses NF-kB Activation Through Inhibition of IkBa Phosphorylation and Degradation. Sekhar Majumdar and Bharat B. Aggarwal. J. Immunol., 167: 2911-2920 (2001).
5. Tumor Suppressor MMAC/PTEN Inhibits Cytokine-induced NF-kB Activation without Interfering with the IkB Degradation Pathway. Dimpy Koul, Yixin Yao, James L. Abbruzzese, W. K. Alfred Yung, and Shrikanth A. G. Reddy. J. Biol. Chem, 276: 11402-11408 (2001).
6. IFN-a Suppresses Activation of Nuclear Transcription Factors NF-kB and Activator Protein 1 and Potentiates TNF-Induced Apoptosis. Sunil K. Manna, Asok Mukhopadhyay, and Bharat B. Aggarwal. J. Immunol., 165: 4927-4934 (2000).
7. IKKa Provides an Essential Link between RANK Signaling and Cyclin D1 Expression during Mammary Gland Development. Yixue Cao, Giuseppina Bonizzi, Tiffany N. Seagroves, Florian R. Greten, Randall Johnson, Emmett V. Schmidt, and Michael Karin. Cell, 107, 763-775 (2001).
8. The Lymphotoxin-b Receptor Induces Different Patterns of Gene Expression via Two NF-kB Pathways . Emmanuel Dejardin, Nathalie M. Droin, Mireille Delhase, Elvira Haas, Yixue Cao, Constantin Makris, Zhi-Wei Li, Michael Karin, Carl F. Ware and Douglas R. Green. Immunity 17: 525-535 (2002).
9. Adenosine suppresses activation of nuclear factor- B selectively induced by tumor necrosis factor in different cell types. Sekhar Majumdar, Bharat B Aggarwal Oncogene 22, 1206-1218 (2001)
10. Piceatannol Inhibits TNF-Induced NF-kB Activation and NF-kB-Mediated Gene Expression Through Suppression of IkBa Kinase and p65 Phosphorylation. Kazuhiro Ashikawa, Sekhar Majumdar, Sanjeev Banerjee, Alok C. Bharti, Shishir Shishodia, and Bharat B. Aggarwal . J. Immunol., 169: 6490–6497 (2002).
11. Cigarette smoke condensate activates nuclear transcription factor-kB through phosphorylation and degradation of IkB : correlation with induction of cyclooxygenase-2. Ruby John Anto, Asok Mukhopadhyay, Shishir Shishodia, C. Gary Gairola, and Bharat B. Aggarwal. Carcinogenesis, 23: 1511-1518 (2002).
12. Thalidomide Suppresses NF-kB Activation Induced by TNF and H2O2, But Not That Activated by Ceramide, Lipopolysaccharides, or Phorbol Ester. Sekhar Majumdar, Betty Lamothe, and Bharat B. Aggarwal. J. Immunol.,168: 2644-2651 (2002).
13. Complete Reconstitution of Human IkB Kinase (IKK) Complex in Yeast. Assessment of its stoichiometry and the role of ikk on the complex activity in the absence of stimulation. Beth Schomer Miller and Ebrahim Zandi. J. Biol. Chem, 276: 36320 – 36326 (2001).
14. Leflunomide Suppresses TNF-Induced Cellular Responses: Effects on NF-kB, Activator Protein-1, c-Jun N-Terminal Protein Kinase, and Apoptosis. Sunil K. Manna, Asok Mukhopadhyay, and Bharat B. Aggarwal. J. Immunol., 165: 5962-5969 (2000).
15. A recessive mutant cell line with a constitutive IkB kinase activity.  Chinanonwait N, H Miura, N Yamamoto, S Yamaoka. FEBS Letters 531:553-560 (2002).
WB (TK26 cells), Fig. 2c
WB (TK26 and M319-5 cells treated with cycloheximide), Fig. 3c
WB (B5, TK26, and hybrid TK26--Rat-1 cells), Fig. 6b

16. The two faces of IKK and NF-kB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Lee-Wei Chen, Laurence Egan, Zhi-Wei Li, Florian R. Greten, Martin F. Kagnoff, Michael Karin. Nature Medicine 9, 575-581 (2003).
17. Ursolic Acid Inhibits Nuclear Factor-B Activation Induced by Carcinogenic Agents through Suppression of IkB Kinase and p65 Phosphorylation: Correlation with Down-Regulation of Cyclooxygenase 2, Matrix Metalloproteinase 9, and Cyclin D.  Shishir Shishodia, Sekhar Majumdar, Sanjeev Banerjee, and Bharat B. Aggarwal. Cancer Res. 63: 4375-4383 (2003).
18. Two Carboxyl-terminal Activation Regions of Epstein-Barr Virus Latent Membrane Protein 1 Activate NF-kB through Distinct Signaling Pathways in Fibroblast Cell Lines. Naohito Saito, Gilles Courtois, Ayako Chiba, Norio Yamamoto, Takeshi Nitta, Noriko Hironaka, Martin Rowe, Naoki Yamamoto, and Shoji Yamaoka. J. Biol. Chem., 278: 46565-46575 (2003).
19. Flavopiridol inhibits NF-kB activation induced by various carcinogens and inflammatory agents through inhibition of IkB kinase and p65 phosphorylation: Abrogation of cyclin D1, cyclooxygenase-2 and matrix metalloprotease-9.  Yasunari Takada and Bharat B. Aggarwal. J. Biol. Chem., Nov 2003; 10.1074/jbc.M304546200.
20. Identification of a p65 peptide that selectively inhibits NF-kB activation induced by various inflammatory stimuli and its role in downregulation of NF-kB-mediated gene expression and upregulation of apoptosis. Yasunari Takada, Sujay Singh, and Bharat B. Aggarwal. J. Biol. Chem., Jan 2004; 10.1074/jbc.M311192200. IkB kinase-a acts in the epidermis to control skeletal and craniofacial morphogenesis. K. Sil, Shin Maeda, Yuji Sano, Dennis R. Roop, Michael Karin. Nature428, 660 - 664 (08 Apr 2004) Letters to Nature
21. Protein farnesyltransferase inhibitor (SCH 66336) abolishes NF-kappa B activation induced by various carcinogens and inflammatory stimuli leading to suppression of NF-kappaB-regulated gene expression and upregulation of apoptosis.Yasunari Takada, Fadlo Khuri, and Bharat B. Aggarwal. J. Biol. Chem., Apr 2004; 10.1074/jbc.M400963200.
22. Cyclooxygenase (COX)-2 Inhibitor Celecoxib Abrogates TNF-Induced NF-kB Activation through Inhibition of Activation of IkB Kinase and Akt in Human Non-Small Cell Lung Carcinoma: Correlation with Suppression of COX-2 Synthesis. Shishir Shishodia, Dimpy Koul, and Bharat B. Aggarwal. J. Immunol., 173: 2011-2022 (2004).
23. Guggulsterone inhibits NF-kB and IkBa kinase activation, suppresses expression of antiapoptotic gene products and enhances apoptosis. Shishir Shishodia and Bharat B Aggarwal. J. Biol. Chem., Aug 2004; 10.1074/jbc.M408093200.
24. Genetic Deletion of Glycogen Synthase Kinase-3 Abrogates Activation of IkB Kinase, JNK, Akt, and p44/p42 MAPK but Potentiates Apoptosis Induced by Tumor Necrosis Factor. Yasunari Takada, Xianjun Fang, Md. Saha Jamaluddin, Douglas D. Boyd, and Bharat B. Aggarwal. J. Biol. Chem., 279: 39541-39554 (2004).
25. Iron-mediated H2O2 Production as a Mechanism for Cell Type-specific Inhibition of Tumor Necrosis Factora-Induced but Not Interleukin-1-induced IkB Kinase Complex/Nuclear Factor-kB Activation. Andreas Panopoulos, Maged Harraz, John F. Engelhardt, and Ebrahim Zandi. J. Biol. Chem., 280: 2912-2923 (2005).   
26. Identification of a Novel Blocker of IkB Kinase That Enhances Cellular Apoptosis and Inhibits Cellular Invasion through Suppression of NF-kB-Regulated Gene Products. Haruyo Ichikawa, Yasunari Takada, Akira Murakami, and Bharat B. Aggarwal.  J. Immunol., 174: 7383- 392 (2005).   
27. Identification of a Novel Blocker of IkB Kinase That Enhances Cellular Apoptosis and Inhibits Cellular Invasion through Suppression of NF-kB-Regulated Gene Products. Haruyo Ichikawa, Yasunari Takada, Akira Murakami, and Bharat B. Aggarwal.  J. Immunol., 174: 7383-7392 (2005).   
28. IkB kinase (IKK)ß, but not IKK, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss. Maria Grazia Ruocco, Shin Maeda, Jin Mo Park, Toby Lawrence, Li-Chung Hsu, Yixue Cao, Georg Schett, Erwin F. Wagner, and Michael Karin. J. Exp. Med., 201: 1677-1687 (2005).   
29. Nurse like cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1. Mitsufumi Nishio, Tomoyuki Endo, Nobuhiro Tsukada, Junko Ohata, Shinichi Kitada, John C. Reed, Nathan J. Zvaifler, and Thomas J. Kipps. Blood, 106: 1012 - 1020 (2005).
30. Curcumin (diferuloylmethane) inhibits constitutive NF-kB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Shishir Shishodia, Hesham M. Amin, Raymond Lai and Bharat B. Aggarwal. Biochemical Pharmacology, Volume 70 (5): 700-713 (2005).
31. Nurse like cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1. Mitsufumi Nishio, Tomoyuki Endo, Nobuhiro Tsukada, Junko Ohata, Shinichi Kitada, John C. Reed, Nathan J. Zvaifler, and Thomas J. Kipps. Blood, 106: 1012-1020 (2005).
32. N-(4-Hydroxyphenyl)Retinamide Inhibits Invasion, Suppresses Osteoclastogenesis, and Potentiates Apoptosis through Down-regulation of IkB Kinase and Nuclear Factor-kB–Regulated Gene Products. Shishir Shishodia, Angelica M. Gutierrez, Reuben Lotan, and Bharat B. Aggarwal. Cancer Res., 65: 9555-9565 (2005).
33. Guggulsterone Inhibits Osteoclastogenesis Induced by Receptor Activator of Nuclear Factor-kB Ligand and by Tumor Cells by Suppressing Nuclear Factor-kB Activation. Haruyo Ichikawa and Bharat B. Aggarwal. Clin. Cancer Res., 12: 662-668 (2006).
34. Skin lesion development in a mouse model of incontinentia pigmenti is triggered by NEMO deficiency in epidermal keratinocytes and requires TNF signaling. Arianna Nenci, Marion Huth, Alfred Funteh, Marc Schmidt-Supprian, Wilhelm Bloch, Daniel Metzger, Pierre Chambon, Klaus Rajewsky, Thomas Krieg, Ingo Haase, and Manolis Pasparakis. Hum. Mol. Genet., 15: 531-542 (2006).
35. Notch3 and pre-TCR interaction unveils distinct NF-êB pathways in T-cell development and leukemia. Alessandra Vacca, Maria Pia Felli, Rocco Palermo, Giuseppina Di Mario, Angelica Calce, Monica Di Giovine, Luigi Frati, Alberto Gulino, Isabella Screpanti. The EMBO Journal advance online publication 23 February 2006;
doi: 10.1038/sj.emboj.7600996
36. A Point Mutation in NEMO Associated with Anhidrotic Ectodermal Dysplasia with Immunodeficiency Pathology Results in Destabilization of the Oligomer and Reduces Lipopolysaccharide-and Tumor Necrosis Factor-mediated NF-kB Activation. Emilie Vinolo, Hélène Sebban, Alain Chaffotte, Alain Israël, Gilles Courtois, Michel Véron, and Fabrice Agou. J. Biol. Chem., 281: 6334-6348 (2006).
37. Suberoylanilide Hydroxamic Acid Potentiates Apoptosis, Inhibits Invasion, and Abolishes Osteoclastogenesis by Suppressing Nuclear Factor-kB Activation. Yasunari Takada, Ann Gillenwater, Haruyo Ichikawa, and Bharat B. Aggarwal. J. Biol. Chem., 281: 5612-5622 (2006).
38. Epithelial Cell IkB-Kinase  Has an Important Protective Role in Clostridium difficile Toxin A-Induced Mucosal Injury. Sungwon Chae, Lars Eckmann, Yukiko Miyamoto, Charalabos Pothoulakis, Michael Karin, and Martin F. Kagnoff. J. Immunol., 177: 1214-1220 (2006).
39. Plumbagin (5-Hydroxy-2-methyl-1,4-naphthoquinone) Suppresses NF-kB Activation and NF-kB-regulated Gene Products Through Modulation of p65 and IkB Kinase Activation, Leading to Potentiation of Apoptosis Induced by Cytokine and Chemotherapeutic Agents. Santosh K. Sandur, Haruyo Ichikawa, Gautam Sethi, Kwang Seok Ahn, and Bharat B. Aggarwal. J. Biol. Chem., 281: 17023-17033 (2006).
40. Indirubin enhances TNF-induced apoptosis through modulation of nuclear factor-B signaling pathway. Gautam Sethi, Kwang Seok Ahn, Santosh K. Sandur, Xin Lin, Madan M. Chaturvedi, and Bharat B. Aggarwal. J. Biol. Chem., Jun 2006; 10.1074/jbc.M602627200.
41. Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-kB activation and proliferation in human head and neck squamous cell carcinoma. D G Jackson-Bernitsas, H Ichikawa, Y Takada, J N Myers, X L Lin, B G Darnay, M M Chaturvedi, B B Aggarwal. Oncogene (04 Sep 2006) online publication.
42. Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch. Rebecca J Richardson, Jill Dixon, Saimon Malhotra, Matthew J Hardman, Lynnette Knowles, et al. Nature Genetics  Published online: 15 October 2006; | doi:10.1038/ng1894

43. An efficient tandem affinity purification procedure for interaction proteomics in mammalian cells. Tilmann Buerckstaemmer, Keiryn L Bennett, Adrijana Preradovic, Gregor Schuetze, Oliver Hantschel, Giulio Superti-Furga, Angela Bauch. Nature Methods (22 Oct 2006).
44. Hepatocyte-specific IKKy/NEMO expression determines the degree of liver injury. Beraza M, T Ludde, U Assmus, T Roskams, S Vander Borght, C Trautwein. Gastroenterology 132: 2504-2517 (2007).  Imgenex products cited:
1. IMG-129A (IKKb/IKK2): IP (mouse liver proteins), Fig. 1E; Tab. 1.
2. IMG-136A (IKKa/IKK1): WB (mouse live proteins), Fig. 1E.
45. Activation of intrinsic and extrinsic proapoptotic signaling pathways in interleukin-18-mediated human cardiac endothelial cell death. B Chandrasekar, K Vemula, RM Surabhi, M Li-Weber, LB Owen-Schaub, LE Jensen, and S Mummidi. J Biol Chem 279:20221-20233. (2004). WB (human cardiac microvascular endothelial cells), Fig. 2G.
46. Identification of a p65 peptide that selectively inhibits NF-κB activation induced by various inflammatory stimuli and its role in down-regulation of NF-κB-mediated gene expression and up-regulation of apoptosis. Takada Y, S Singh, B Aggarwal. J Biol Chem 279: 15096-15104 (2004). Imgenex antibodies cited [WB (human leukemic cell line KBM-5 cells), Fig. 5C]:
1. IKKα/IKK1 (IMG-136A)
2. Ikkβ/IKK2 (IMG-129A)
47. Inhibition of I_kB kinase-nuclear factor-_kB signaling pathway by 3,5-Bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog curcumin. Kasinski A, Du Y, Thomas S, Zhao J, Sun S, Khuri F, Wang C, Shoji M, Sun A, Synder J, Liotta D, Fu H. Mol Phamacol 74:654-661 (2008). Imgenex antibodies cited:
1. IKK_a/IKK1 (IMG-136A): IP (human A549 cells), immunoprecipitated cytoplasmic extracts were used for IKK kinase assays.
2. IKK_b/IKK2 (IMG-129A):WB (human A549 cells), Fig. 5a; 6a,b.
48. Coronarin D, a labdane diterpene, inhibits both constitutive and inducible nuclear factor-κB pathway activation, leading to potentiation of apoptosis, inhibition of invasion, and suppression of osteoclastogenesis.  Kunnumakkara A, H Ichikawa, P Anand, C Mohankumar, P Hema, M Nair, B Aggarwal. Molecular Cancer Therapeutics 7: 3306-3317 (2008). Imgenex antibodies cited:
1. IKKα/IKK1 (IMG-136A): WB (human KMB-5 cells), Fig. 2C.
2. IKKb/IKK2 (IMG-129A): WB (human KMB-5 cells), Fig. 2C.
49. Opposing functions of IKKβ during acute and chronic intestinal inflammation. Eckmann L, T Nebelsiek, A Fingerle, S Dann, J Mages, R Lang, S Robine, M Kagnoff, R Schmid, M Karin, M Arkan, F Greten. PNAS 105: 15058-15063 (2008). WB (mouse colon cells), Fig. 4A.
50. BAFF activates Akt and Erk through BAFF-R in an IKK₁-dependent manner in primary mouse B cells. Otipoboy K, Y Sasaki, M Schmidt-Supprian, A Patke, R Gareus, M Pasparakis, A BTarakovsky, K Rajewsky.  PNAS 105: 12435-12438 (2008). WB (mouse splenic B cells), Fig. 1B.
51. Berberine modifies cysteine 197 of IκBα kinase, suppresses nuclear factor-_κB-regulated antiapoptotic gene products, and potentiates apoptosis.  Pandey M, B Sung, A Kunnumakkara, G Sethi, M Chaturvedi, B Aggarwal.  Cancer Research 68: 5370-5379 (2008). Imgenex antibodies cited:
1. IMG-136A (IKKa/IKK1): WB (human multiple myeloma U266 cells), Fig. 3A,C.
2. IMG-129A (IKKb/IKK1): WB (human multiple myeloma U266 cells), Fig. 3A,C.
52. HTLV-1 tax is a critical lipid raft modulator that hijacks I_kB kinases to the microdomains for persistent activation of NF_kB.  Huang J, T Ren, H Guan, Y Jiang, H Cheng.  JBC 284: 8208-6217 (2009).  Imgenex antibodies cited:
1. IMX-5142 (IkBa- Sera): WB (human T cell lines), Fig. 1B.
2. IMG-136A (IKKa/IKK1): WB (human T cell lines), Figs. 1E,D,G; 2A; 3D,E,F,G; 4B,F; 6C,D; 7C,D,G.
3. IMG-129A (IKKb/IKK2): WB (human T cell lines), Figs. 1E,D,G; 2A; 3D,E,F,G; 4B,F; 6C,D; 7C,D,G.
53. Escin, a pentacyclic triterpene, chemosensitizes human tumor cells through inhibition of nuclear factor-kB signaling pathway. Harikumar K, B Sung, M Pandey, S Guha, S Krishnan, B Aggarwal. Mol Pharma 77: 818-827 (2010). The following monoclonal antibodies were used in western blot; human chronic myeloid leukemia KBM-5 cell line, Fig 4.
1. IKKB/IKK2 (IMG-129A)
2. IKKa/IKK1 (IMG-136A)
3. IKBalpha (IMG-127A) 
4. IKKgamma (IMG-324A & IMG-287A)