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Antibodies from IMGENEX: NF-kB Pathway

NF-kB (Nuclear Factor-KappaB) is a heterodimeric protein composed of different combinations of members of the Rel family of transcription factors. The Rel/NF-kB family of transcription factors are involved mainly in stress-induced, immune, and inflammatory responses. In addition, these molecules play important roles during the development of certain hemopoietic cells, keratinocytes, and lymphoid organ structures. More recently, NF-kB family members have been implicated in neoplastic progression and the formation of neuronal synapses. NF-kB is also an important regulator in cell fate decisions, such as programmed cell death and proliferation control, and is critical in tumorigenesis (Ref.1).

NF-kB is composed of homo- and heterodimers of five members of the Rel family including NF-kB1(p50), NF-kB2 (p52), RelA (p65), RelB, and c-Rel (Rel). Hetero and Homo-dimerization of NF-kB proteins which exhibit differential binding specificities includes p50/RelA, p50/c-Rel, p52/c-Rel, p65/c-Rel, RelA/RelA, p50/p50, p52/p52, RelB/p50 and RelB/p52. All the Rel proteins contain a conserved N-terminal region, called the RHD (Rel Homology Domain). The N-terminal part of the RHD contains the DNA-binding domain, whereas the dimerization domain is located in the C-terminal region of the RHD. Close to the C-terminal end of the RHD lies the NLS (Nuclear Localization Signal), which is essential for the transport of active NF-kB complexes into the nucleus. NF-kB1 and RelA were the first NF-kB proteins to be identified. Their N-terminal 300 AA revealed high similarity to the oncoprotein v-Rel, its cellular homologue c-Rel and the Drosophila protein Dorsal what resulted in the terms Rel proteins and RHD. The Rel/NF-kB proteins can be divided into two groups: Only RelA (p65), RelB and c-Rel (and Dorsal and Dif in Drosophila) contain potent TDs (Transactivation Domains) within sequences C-terminal to the RHD. The TDs consist of abundant serine, acidic and hydrophobic aminoacids that are essential for transactivation activity. In contrast, p50 and p52 do not possess TDs, and therefore cannot act as transcriptional activators by themselves. NF-kB1and NF-kB2 are produced as p105 and p100 precursors, respectively. The NF-kB1 p105 precursor appears to undergo constitutive processing by the cellular proteasome that removes the C-terminal I-kB-like portion to generate p50. NF-kB2 p100 precursor can be processed to remove the I-kB-like C-terminus, allowing the active p52 N-terminal half to function in transcriptional regulation. Homo- or heterodimers of p50 and p52 were even reported to repress KappaB site-dependent transcription, possibly by competing with other transcriptionally active dimers (e.g. p50/RelA) for DNA binding (Ref.2).

NF-kB dimers are sequestered in the cytosol of unstimulated cells via non-covalent interactions with a class of inhibitor proteins, called IkBs. To date seven IkBs have been identified: IkB-alpha, IkB-beta, IkB-gamma, IkB-epsilon, BCL3, p100 and p105. All known IkBs contain multiple copies of a 30-33 aa sequence, called ankyrin repeats which mediate the association between IkB and NF-kB dimers. The ankyrin repeats interact with a region in the RHD of the NF-kB proteins and by this mask their NLS and prevent nuclear translocation. Signals that induce NF-kB activity cause the phosphorylation of IkBs, their dissociation and subsequent degradation, thereby allowing activation of the NF-kB complex. Activated NF-kB complex translocates into the nucleus and binds DNA at kB-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y is a C or T pyrimidine) and induce gene expression. The degradation of IkB proteins that permits NF-KappaB molecules to move into the nucleus is also carried out by the proteasome but only after prior phosphorylation of IkB by the IKK (IkB Kinase Complex). The IKK is composed of three subunits: two, IKK-alpha (IKK1) and IKK-beta (IKK2), are bonafide kinases, while the third, IKK-gamma (NEMO), has no catalytic activity but plays a critical regulatory role. IKK-alpha is the predominant IkB kinase. Phosphorylated IkB is recognized by Beta-TrCP, a component of the SCF (skp-1/Cul/F box) ubiquitin ligase complex that mediates poly-ubiquitination of I-kB and its subsequent proteasomal degradation. In contrast, IKK-alpha mediates the phosphorylation-dependent processing of p100, resulting in the generation of p52 (Ref.3).

NF-kB can be activated by exposure of cells to LPS (Lipopolysaccharides) or inflammatory cytokines such as TNF (Tumour Necrosis Factor) or IL-1 (Interleukin-1), growth factors, lymphokines, oxidant-free radicals, inhaled particles, viral infection or expression of certain viral or bacterial gene products, UV irradiation, B or T-Cell activation, and by other physiological and non physiological stimuli. The most potent NF-kB activators are the proinflammatory cytokines IL-1 and TNF, which cause rapid phosphorylation of kBs at two sites within their N-terminal regulatory domain. TNF, which is the best-studied activator, binds to its receptor and recruits a protein called TRADD (TNF-Associated Receptor Death Domain). TRADD binds to the TRAF2 (TNF Receptor-Associated Factor-2) that recruits NIK (NF-kB-Inducible Kinase). Both IKK1 and IKK2 have canonical sequences that can be phosphorylated by the MAP (Mitogen Activated Protein) kinase NIK/MEKK1 and both kinases can independently phosphorylate IkB-alpha or IkB-beta. TRAF2 also interacts with A20, a zinc finger protein whose expression is induced by agents that activate NF-kB. A20 functions to block TRAF2-mediated NF-kB activation. A20 also inhibits TNF and IL-1 induced activation of NF-KappaB suggesting that it may act as a general inhibitor of NF-kB activation. CD40, another member of the TNF receptor family, can signal the induced processing of p100 to p52. The ligand for CD40, CD40L (CD154), is expressed on activated CD4-T cells, and when it engages CD40 in a T:B interaction, can induce B-Cell proliferation and differentiation. CD40 signaling induces p100 processing through NIK in the non-canonical pathway. LT-BetaR (Lymphotoxin–Beta Receptor), which is critically important for the development and organization of lymphoid tissue also gives way to two separate pathways, one that activates the canonical NF-KappaB pathway and depends upon IKK-beta and IKK-gamma/NEMO and another that induces p100 processing dependent on NIK and IKK-alpha (Ref.4).

The recognition of bacterial and viral products by Toll-like receptors on cells of the innate immune system also results in NF-kB induction, leading to the production of proinflammatory cytokines and the activation of Antigen Presenting Cell for T-Cell costimulation in the adaptive immune response. Viral infection leads to the increased expression and secretion of the cytokine interferon gamma (IFN-gamma) from host cells. IFN-gamma activates the double-stranded RNA (dsRNA)-dependent serine-threonine protein kinase R (PKR). dsRNA produced during viral replication induces PKR dimerization, autophosphorylation, and activation of the eIF-2alpha kinase activity. When eIF-2alpha is phosphorylated, cellular and viral protein translation cannot efficiently occur. Alternatively, bacterial products or cellular stress can also activate PKR by an endogenous gene product called PACT. The binding of PACT to PKR promotes conformational changes that allow PKR to activate the downstream signaling pathways leading to the activation of NF-KappaB. Several survival and stimulatory factors that is important in the dev


Baldwin AS Jr.
The NF-kappa B and I kappa B proteins: new discoveries and insights.
Annu Rev Immunol. 1996;14:649-83.
PMID: 8717528

Vigo Heissmeyer, Daniel Krappmann, Eunice N. Hatada, and Claus Scheidereit.
Shared Pathways of I B Kinase-Induced SCF TrCP-Mediated Ubiquitination and Degradation for the NF- B Precursor p105 and I B. Molecular and Cellular Biology, February 2001, p. 1024-1035, Vol. 21, No. 4 PMID: 11158290

Baeuerle, P. A.
I-kappa-B--NF-kappa-B structures: at the interface of inflammation control. Cell 95: 729-731, 1998. PubMed ID : 9865689

Joel L. Pomerantz and David Baltimore.
Two pathways to NF-KappaB.
Molecular Cell, Vol. 10, 693-701, October 2002.
PMID: 12419209

Fulvio D'Acquisto, and Sankar Ghosh.
PACT and PKR: Turning on NF- B in the Absence of Virus. Science's STKE, 3 July 2001.PMID: 11752660

Vishva Dixit and Tak. W. Mak.
NF-KappaB signaling: Many Roads Lead To Madrid. Cell, Vol. 111, 615-619, November 27, 2000 PMID: 12464174

Nanxin Li and Michael Karin.
Ionizing radiation and short wavelength UV activate NF-KappaB through two distinct mechanisms. Proc. Natl. Acad. Sci. USA, Vol.95, pp. 13012-13017, October 1998. PMID: 9789032

Markus Müller, Alessandro Morotti, and Carola Ponzetto. Activation of NF- B Is Essential for Hepatocyte Growth Factor-Mediated Proliferation and Tubulogenesis. Molecular and Cellular Biology, February 2002, p. 1060-1072, Vol. 22, No. 4 PMID: 11809798

Michael Hinz, Daniel Krappmann, Alexandra Eichten, Andreas Heder, Claus Scheidereit, and Michael Strauss.
NF- B Function in Growth Control: Regulation of Cyclin D1 Expression and G0/G1-to-S-Phase Transition.Molecular and Cellular Biology, April 1999, p. 2690-2698, Vol. 19, No. 4 PMID: 10082535

Primary Search

NF-KappaB, Nuclear Factor-KappaB, NF-KappaB1, p50, NF-KappaB2, p52, RelA, p65, RelB, c-Rel, Rel, RHD, Rel Homology Domain, NLS, Nuclear Localization Signal, TDs, Transactivation Domains, IKK-alpha, IKK1, IKK-beta, IKK2, LPS, Lipopolysaccharides, TNF, Tumour Necrosis Factor, TNFR, TNF Receptor, IL-1, IL-1R, Interleukin-1, GF, Growth Factors, Lymphokines, Oxidant-Free Radicals, Inhaled Particles, Viral Infection, Certain Viral or Bacterial Gene Products, UV Irradiation, B or T Cell Activation, TRADD, TNF-Associated Receptor Death Domain, TRAF2, TNF Receptor-Associated Factor-2, NIK, NF-KappaB Inducible Kinase, MAP, Mitogen Activated Protein, PKR, Protein Kinase-R, ERK1/2, Extracellular Signal-Regulated Kinases-1/2 p38 MAPK, FADD, Fas Associated Death Domain, IRAK, IL-1 Receptor-Associated Kinases, RIP, Receptor-Interacting Protein, TRAFs, TNF Receptor-Associated Factors, MyD88, Myeloid Differentiation Primary Response Gene-88, TollIP, Toll-Interacting Protein, TAK1, TGF-Beta-Activating Kinase-1, Fyn, Lyn, PKC, Protein Kinase-C, IKK Complex, IKK-Alpha, IKK-Beta, IKK-Gamma, BAFF, B-cell Activation Factor, HGF, Hepatocyte Growth Factor, APC, Antigen Presenting Cell, CBP, CREB Binding Protein, p300.

Secondary Search
MALP, Mycoplasmal macrophage-Activating Lipopeptide, PGN, Peptidoglycans, PI3K, Phosphoinositide-3-Kinase, Akt, Cyclin-D1, Vav, ZAP70, Zeta-Chain-Associated Protein Kinase 70, BIMP, BCL10, MALT, Mucosa Associated Lymphoid Tissue Lymphoma Translocation Gene, BLK, B Lymphoid Tyrosine Kinase.

Transcription Regulation, Cell Signaling.

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Found 217 results, displaying 1 to 50 | Show all
Cat.No Description Format Species Clone Application Publications
IMG-5028 Caspase-1 Purified H, M 14F468 IHC (p), WB pricing
IMG-136A IKK alpha Purified H, M, Mk 14A231 Flow (I), IHC (p), IP, WB pricing
IMG-161A A20 (TNFAIP3) Purified H, M, R 59A426 Flow (I), IF/ICC, IHC (p), IP, WB pricing
IMG-434 ABIN-2 Purified H, M, R N/A WB pricing
IMG-563 ACT1 (CIKS, TRAF3IP2) Purified H, M N/A   IHC (p), WB pricing
IMG-284 ACT1/CIKS - discontinued, please see IMG-563 Purified H N/A WB pricing
IMG-487 AKT1 Purified H N/A WB pricing
IMG-5411-1 AKT1 Purified, Peptide Affinity H, M, R N/A IHC (p), WB pricing
IMG-5411-2 AKT1 Purified, Peptide Affinity H, M, R N/A IHC (p), WB pricing
IMG-187A AKT1 (Ser473) Purified H, M 104A282 IF/ICC, IP, WB pricing
IMG-187E AKT1 (Ser473) Azide-Free H, M 104A282 IF/ICC, IP, WB pricing
IMG-351 AKT2 Ascites H 95C657.1.2 WB pricing
IMG-421 AKT2/3 Purified H N/A WB pricing
IMG-326 AKT3 Purified H, M, R 66C1247.1 WB pricing
IMG-355 AKT3 Purified H, M, R N/A WB pricing
IMG-3389 AKT3 Purified, Peptide Affinity H N/A WB pricing
IMX-6347 ARAP1 Sera C, D, H, Mk, M, R N/A Peptide ELISA pricing
IMG-90221-1 ATM (Ser1981) Purified, Peptide Affinity H, M N/A IHC (p) pricing
IMG-497 Bcl-3 Purified H N/A WB pricing
IMG-247 BLyS/BAFF/THANK/TALL-1 Purified H, M N/A WB pricing
IMG-5610-1 BLyS/BAFF/THANK/TALL-1 (CT) Purified H, M, R N/A WB pricing
IMG-5610-2 BLyS/BAFF/THANK/TALL-1 (CT) Purified H, M, R N/A WB pricing
IMX-6345 BMI1 Sera Chp, Hs, H, Mk N/A Peptide ELISA pricing
IMG-6714A Cactin Purified Chp, C, D, H, O, RH, W N/A IHC (p), WB pricing
IMX-5160 CARMA1/ CARD11 Sera H         Peptide ELISA pricing
IMX-5161 CARMA1/ CARD11 Sera H       Peptide ELISA pricing
ABU007 CARMA1/CARD11 Antibody Bundle Sera H N/A Peptide ELISA pricing
IMG-5025 Caspase-1 Purified H N/A IHC (p), WB pricing
IMG-6542A CD27 Purified H 203.6 Flow (CS), IF/ICC, IHC (frozen) pricing
IMG-5447-1 CIKS/Act1 (NT) Purified, Peptide Affinity H N/A WB pricing
IMG-5447-2 CIKS/Act1 (NT) Purified, Peptide Affinity H N/A WB pricing
IMG-6279A CUEDC2 Purified Chp, C, D, Hs, H, M, Pi, RH N/A WB pricing
IMG-6299A CUEDC2 Purified H N/A IHC (p) pricing
IMG-5618-1 ECSIT (CT) Purified H, M N/A WB pricing
IMG-5618-2 ECSIT (CT) Purified H, M N/A WB pricing
IMG-90565-2 eIF2a (Ab-51) Purified, Peptide Affinity H, M, R N/A IHC (p), WB pricing
IMG-90331-1 eIF2a (Ser51) Purified, Peptide Affinity H, M, R N/A IHC (p), WB pricing
IMG-90124-1 GSK3a (Ser21) Purified, Peptide Affinity H, M, R N/A IHC (p), WB pricing
IMG-90581-2 GSK3b (Ab-216) Purified, Peptide Affinity H, M, R N/A WB pricing
IMG-90343-1 GSK3b (Tyr216) Purified, Peptide Affinity H, M, R N/A IHC (p), WB pricing
IMG-90468-2 HDAC-2 (Ab-394) Purified, Peptide Affinity H, M, R N/A IHC (p), WB pricing
IMG-90275-1 HDAC-4 (Ser632) Purified, Peptide Affinity H, M, R N/A WB pricing
IMG-90470-2 HDAC-5 (Ab-498) Purified, Peptide Affinity H, M, R N/A IHC (p), WB pricing
IMG-90276-1 HDAC-5 (Ser498) Purified, Peptide Affinity H, M, R N/A IHC (p), WB pricing
IMG-90471-2 HDAC-8 (Ab-39) Purified, Peptide Affinity H N/A IHC (p), WB pricing
IMG-90227-1 HDAC-8 (Ser39) Purified, Peptide Affinity H, M, R N/A IHC (p) pricing
IMG-5112A HNLF Purified M, H, R N/A WB pricing
IMG-4047 IKAP Purified H N/A WB pricing
IMG-127A IkB alpha (IkBa) Purified H, M 6A920 Flow (I), IHC (p), IP, WB pricing
IMG-5016 IkB alpha (IkBa) Purified H N/A IHC (p), WB pricing






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