Regulating Immune Response Pathways with IKK beta

Wed, 01/29/2014 - 14:52

IKK beta, also known as IKK2, activates the NFkB complex by phosphorylating the NFkB inhibitor, IkBa. Several transcript variants, some protein-coding and some not, have been found for IKKB. The Nuclear Factor-kappa B (NF-kB) family of transcription factors regulates the expression of a wide range of genes critical for immune and inflammatory responses, cell survival, immune development, and cell proliferation (1). NF-kB was firstly identified by Dr. Ranjan Sen in the lab of Nobel Prize laureate David Baltimore as a regulator of kB light chain expression in mature B and plasma cells (2). Years of research following this discovery demonstrated that NF-kB is expressed in almost all cell types and tissues, and specific NF-kB binding sites are present in the promoters/enhancers of a large number of genes.

The NF-kB family contains five structurally related members named p50 and p52 (the N-terminal fragments of the longer NFkB/p105 and NFkB/p100 proteins, respectively), p65 (RelA), c-Rel, and RelB. These proteins either homo- or heterodimerize to form transcriptionally active (e.g, p50-p65) or repressive (e.g., p50-p50) NF-kB dimers. The activity of NF-kB is tightly regulated by interaction with inhibitory IkB proteins. As with the NF-kB transcription factors, there are several IkB proteins (e.g., IkB alpha, IkB beta, IkB gamma, IkB epsilon).

In most cells, NF-kB is present as a latent, inactive, IkB-bound complex in the cytoplasm. There are two, and possibly three, pathways leading to the activation of NF-kB. The two best-described pathways are called either the canonical and non-canonical pathways or the classical and alternative pathways, respectively. The common upstream regulatory step in both of these pathways is activation of an IkB kinase (IKK) complex (3). The IKK complex contains two catalytic subunits named IKK alpha (IKK1) and IKK beta (IKK2), and a non-catalytic regulatory subunit named IKK gamma or NEMO (NF-kB essential modulator) (4).

Immunohistochemistry-Paraffin: IKK beta Antibody Immunohistochemistry-Paraffin: IKK beta Antibody

Activation of the IKK complex is dependent on the phosphorylation of two serines in the sequence motif SLCTS of the T-loop regions in at least one of the IkB kinases.

In the canonical NF-kB pathway, which is induced by inflammatory cytokines, pathogen-associated molecules, and antigen receptors, IKK beta is both necessary and sufficient to phosphorylate IkB alpha or IkB beta in an IKK gamma-dependent manner (3). IKK alpha and IKK beta share over 50% sequence identity, their domain structures are similar, however despite these sequence and structural similarities, different phenotypes between IKK alpha and IKK beta knockout mice imply distinct physiological roles of the IKK isoforms. IKK beta deficiency results in embryonic death and shows the defective response to inflammatory cytokines and liver cell apoptosis (5). IKK alpha knockout mice display the defective proliferation and differentiation of kerationocyte and the abnormalities of limb and skeleton, suggesting the requirement of the IKK alpha subunit in morphogenesis. Furthermore these two proteins have different sub-cellular localization as well, while IKK beta is predominantly cytoplasmic, IKK alpha has been found to shuttle between the cytoplasm and the nucleus. Considering IKK alpha and IKK beta exist in the same homocomplex, the exact molecular basis for their distinct functions is still unknown (1).

Novus Biologicals offers various types of antibodies against IKK beta, including antibodies, lysates, recombinant proteins, antibody pairs and RNAi, validated in different applications including Western Blot, IHC and Flow Cytometry. IKK beta antibodies can be used as markers to study NF-kB signaling system in both normal and cancerous cells.

  1. PMID: 18626576
  2. PMID: 17114415
  3. PMID: 7072321
  4. PMID: 18267068
  5. PMID: 23343355

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