IKBKB

The following IKBKB reagents supplied by CUSABIO are manufactured under a strict quality control system. Multiple applications have been validated and solid technical support is offered.

IKBKB Antibodies

IKBKB Antibodies for Homo sapiens (Human)

IKBKB Proteins

IKBKB Proteins for Homo sapiens (Human)

IKBKB Proteins for Mus musculus (Mouse)

IKBKB Proteins for Bos taurus (Bovine)

IKBKB Proteins for Rattus norvegicus (Rat)

IKBKB Background

Inhibitory kappa-B kinase subunit beta (IKKβ) is a protein in humans that is encoded by the IKBKB gene. IKKβ, also known as IKK2, is a component of the inhibitory kappa-B kinase (IKK) complex that involved in the nuclear factor kappa B (NF-κB) signaling pathway. Like its closely related to IKKα (IKK1), IKKβ belongs to serine kinase containing leucine zipper and helix-loop-helix protein interaction motifs [1]. Upon pro-inflammatory stimuli such as TNF-α, interleukin-1 (IL-1), and lipopolysaccharide (LPS), various adaptor molecules known as the TNF receptor-associated factors (TRAFs) are recruited. Among these TRAFs, the key enzymes such as MAP/ERK kinase kinase 3 (MEKK3) and transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) specifically phosphorylate and activate IKKβ [2][3]. Activation of IKKβ further evokes the phosphorylation of inhibitory kappa B alpha (IκBα) or IκBβ [4][5], leading to poly-ubiquitination and subsequent degradation of IκB by the proteasome. In resting cells, IκB proteins usually sequester NF-κB in the cytoplasm by masking its nuclear localization sequences (NLSs) [6]. The removal of IκB unmasks the NLS, inducing nuclear translocation of NF-κB and binding to consensus binding sites within promoter regions of specific genes. IKKβ can also mediate phosphorylation of NF-κB p65 to initiate transactivation, leading to increased transcriptional activation following DNA binding [7]. In the nucleus, NF-κB dimers bind to target DNA elements and activate transcription of genes encoding proteins involved in immune response, growth control, or protection against apoptosis [8]. Manolis Pasparakis et al. suggested that the critical function of IKKβ-mediated NF-κB activity in epidermal keratinocytes is to regulate mechanisms that maintain the immune homeostasis of the skin [9]. Canonical IKK2–NF-κB signaling also plays a vital role in the regulation of inflammation and oncogenesis. In addition to the crucial function in NF-κB signaling, IKKβ phosphorylates other substrates and is implicated in the activation of the transcription factor activator protein 1 (AP-1) in response to engagement of CD3 and CD28 coreceptors in CD4+ T cells [10]. Homozygous null mutations of IKBKB gene is found in severe combined immunodeficiency (SCID) patients [11]. And these patients had normal B-cell and T-cell counts but very low levels of immunoglobulins, as well as a severe defect in immune-cell activation that affected both innate and adaptive immune-receptor pathways [11].

[1] Frank Mercurio, Hengyi Zhu, et al. IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation [J]. Science 31 Oct 1997, Vol. 278, Issue 5339, pp. 860-866.
[2] Yang J, Lin Y, et al. The essential role of MEKK3 in TNF-induced NF-kappaB activation [J]. Nat Immunol. 2001 Jul; 2(7):620-4.
[3] Schmidt C, Peng B, et sl. Mechanisms of proinflammatory cytokine-induced biphasic NF-kappaB activation [J]. Mol Cell. 2003 Nov; 12(5):1287-300.
[4] Brown K, Gerstberger S, et al. Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation [J]. Science. 1995 Mar 10; 267(5203):1485-8.
[5] DiDonato J, Mercurio F, et al. Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation [J]. Mol Cell Biol. 1996 Apr; 16(4):1295-304.
[6] Malek S, Chen Y, et al. IkappaBbeta, but not IkappaBalpha, functions as a classical cytoplasmic inhibitor of NF-kappaB dimers by masking both NF-kappaB nuclear localization sequences in resting cells [J]. J Biol Chem. 2001 Nov 30; 276(48):45225-35.
[7] Sakurai H, Chiba H, et al. IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain [J]. J Biol Chem. 1999 Oct 22; 274(43):30353-6.
[8] Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights [J]. Annu Rev Immunol. 1996;14:649-83.
[9] Manolis Pasparakis, Gilles Courtois, et al. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2 [J]. Nature volume 2002, 417, 861-866.
[10] Lupino E, Ramondetti C, et al. IκB kinase β is required for activation of NF-κB and AP-1 in CD3/CD28-stimulated primary CD4(+) T cells [J]. J Immunol 2012;188:2545-2555.
[11] Ulrich Pannicke, Ph.D., et al. Deficiency of Innate and Acquired Immunity Caused by an IKBKB Mutation [J]. N Engl J Med 2013; 369:2504-2514.

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