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NF-kappaB Signalweg

NF-kappaB (nuclear factor k-light-chain-enhancer of activated B cells) ist eine Gruppe homo- und heterodimerischer Transkriptionsfaktoren, die zentraler Bestandteil eines Netzwerks unterschiedlicher Signaltransduktionswege sind. Eine Vielzahl von Signalen, wie etwa Zytokine, Wachstumsfaktoren und Hormone, Infektionen, oxidativer Stress, bestimmte Arzneimittel und chemische Substanzen werden auf die NF-kappaB-Komplexe übertragen und anschließend weitergegeben, um Prozesse wie Zellüberleben, -apoptose und –proliferation sowie Immunantwort und Entzündung zu beeinflussen. Außerdem findet eine Überlagerung mit anderen Signalwegen wie dem MAP-Kinase-Weg und dem p53-Signalweg statt1. Aus diesem Grund sind sie hoch pleiotrop, unter anderem beeinflussen sie eine Reihe phänotypischer Eigenschaften2.

NF-kappaB ist ein homo- oder heterodimerischer Komplex, der in Säugetieren durch die RHD enthaltenden Proteine RelA/p65, RelB, c-Rel, NFKB1/p105/p50 und NFKB2/p100/p52 gebildet wird. Der heterodimerische RELA/p50-Komplex des kanonischen Signalwegs scheint der häufigste zu sein. Alle NF-kappaB-Proteine haben eine N-terminale RHD, die eine bedeutende Rolle bei der DNA-Bindung, als Dimerisationsschnittstelle sowie bei der Bindung an IkappaB-Inhibitoren spielen. NF-kappaB-Proteine variieren allerdings in ihrem C-Terminus: Proteine der Klasse I RELA, RELB und c-Rel beinhalten eine Transaktivierungsdomäne, wohingegen Proteine der Klasse II NFKB1/p105/p50 und NFKB2/p100/p52 eine Ankyrin-Repeat-Transrepressionsdomäne enthalten 3.

Beim kanonischen Signalweg wird NF-KB im Zytoplasma durch die Interaktion mit inhibitorischen IKB-Proteinen in einem inaktiven Zustand gelassen. Nach der Stimulation des NF-kappaB-Signalwegs durch einen der obengenannten Impulse werden diese Regulatoren durch einen IKK-Kinase-Komplex aus den Proteinkinasen IKKalpha, IKKbeta und NEMO phosphoryliert4. Die Phosphorylierung markiert die IkappaB-Inhibitoren für die proteasomale Degradation und setzt somit NF-kappaB frei. Sobald dies stattgefunden hat, wird NF-kappaB weiter durch posttranslationale Modifikation aktiviert und in den Kern verlagert, wo es mit spezifischen KB-Elementen interagiert5 . In Abhängigkeit vom Zelltyp und der Art des empfangenen Reizes wird der nicht-kanonische Signalweg einbezogen. Der Hauptregulator bei diesem Signalweg ist NF-kappaB–induzierende Kinase (NIK), die IKKalpha aktiviert und so zur Phosphorylierung von p100 führt. P100 wird anschließend zu p52 verarbeitet und führt so die Aktivierung und Kernlokalisierung des Dimers p52/RelB NF-kappaB sowie die gezielte Genexpression herbei.

Der kanonische Signalweg hängt nicht von der Proteinsynthese ab und antwortet schnell auf zahlreiche Reize für eine Vielzahl nachgelagerter Auswirkungen. Im Vergleich dazu ist der nicht-kanonische Signalweg langsam und andauernd und antwortet nur auf einen Teil von Signalen für spezifischere Auswirkungen.


1http://www.ncbi.nlm.nih.gov/pubmed/23915189

2http://www.ncbi.nlm.nih.gov/pubmed/21772278

3http://www.ncbi.nlm.nih.gov/pubmed/20066092

4http://www.ncbi.nlm.nih.gov/pubmed/20300203

5http://www.ncbi.nlm.nih.gov/pubmed/21556136

6http://www.ncbi.nlm.nih.gov/pubmed/21173796

Adapter

MYD88 (Myeloid Differentiation Primary Response Gene (88)):

This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal...   More...

TRADD (TNFRSF1A-Associated Via Death Domain):

The protein encoded by this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/TNFR1 and mediates programmed cell death signaling and NF-kappaB activation. This protein binds adaptor protein TRAF2, reduces the recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2, and thus suppresses TRAF2 mediated apoptosis. This protein can also interact with receptor...   More...
Antigene in dieser Kategorie:
KHDRBS1 (KH Domain Containing, RNA Binding, Signal Transduction Associated 1): KHDRBS1 Antikörper KHDRBS1 ELISA Kits KHDRBS1 Proteine
SQSTM1 (Sequestosome 1): SQSTM1 Antikörper SQSTM1 ELISA Kits SQSTM1 Proteine
SLC39A3 (Solute Carrier Family 39 (Zinc Transporter), Member 3): SLC39A3 Antikörper SLC39A3 ELISA Kits SLC39A3 Proteine

Cytokine

IL1A (Interleukin 1 alpha):

The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by monocytes and macrophages as a proprotein, which is proteolytically processed and released in response to cell injury, and thus induces apoptosis. This gene and...   More...

TNF - Tumor Necrosis Factor

This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation,...   More...
Antigene in dieser Kategorie:
CD40LG - CD40 Ligand: CD40LG Antikörper CD40LG ELISA Kits CD40LG Proteine
IL1RN (Interleukin 1 Receptor Antagonist): IL1RN Antikörper IL1RN ELISA Kits IL1RN Proteine
IL1B (Interleukin 1, beta): IL1B Antikörper IL1B ELISA Kits IL1B Proteine
LTB (Lymphotoxin beta (TNF Superfamily, Member 3)): LTB Antikörper LTB ELISA Kits LTB Proteine
TNFSF11 (Tumor Necrosis Factor (Ligand) Superfamily, Member 11): TNFSF11 Antikörper TNFSF11 ELISA Kits TNFSF11 Proteine
TNFSF13B (Tumor Necrosis Factor (Ligand) Superfamily, Member 13b): TNFSF13B Antikörper TNFSF13B ELISA Kits TNFSF13B Proteine

Enzyme

TRAF1 (TNF Receptor-Associated Factor 1):

The protein encoded by this gene is a member of the TNF receptor (TNFR) associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from various receptors of the TNFR superfamily. This protein and TRAF2 form a heterodimeric complex, which is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this...   More...

TRAF2 (TNF Receptor-Associated Factor 2):

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and...   More...
Antigene in dieser Kategorie:
TRAF3 (TNF Receptor-Associated Factor 3): TRAF3 Antikörper TRAF3 ELISA Kits TRAF3 Proteine
TRAF5 (TNF Receptor-Associated Factor 5): TRAF5 Antikörper TRAF5 ELISA Kits TRAF5 Proteine
TRAF6 (TNF Receptor-Associated Factor 6): TRAF6 Antikörper TRAF6 ELISA Kits TRAF6 Proteine

Wachstumsfaktoren

EGF (Epidermal Growth Factor):

This gene encodes a member of the epidermal growth factor superfamily. The encoded protein is synthesized as a large precursor molecule that is proteolytically cleaved to generate the 53-amino acid epidermal growth factor peptide. This protein acts a potent mitogenic factor that plays an important role in the growth, proliferation and differentiation of numerous cell types. This protein acts by...   More...

NGFB (Nerve Growth Factor beta):

This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic...   More...
Antigene in dieser Kategorie:
GH1 - Growth Hormone 1: GH1 Antikörper GH1 ELISA Kits GH1 Proteine
GH2 - Growth Hormone 2: GH2 Antikörper GH2 ELISA Kits GH2 Proteine
INS - Insulin: INS Antikörper INS ELISA Kits INS Proteine
TGFA (Transforming Growth Factor, alpha): TGFA Antikörper TGFA ELISA Kits TGFA Proteine

Inhibitoren

BCL3 (B-Cell CLL/lymphoma 3):

This gene is a proto-oncogene candidate. It is identified by its translocation into the immunoglobulin alpha-locus in some cases of B-cell leukemia. The protein encoded by this gene contains seven ankyrin repeats, which are most closely related to those found in I kappa B proteins. This protein functions as a transcriptional co-activator that activates through its association with NF-kappa B...   More...

NFKBIA (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, alpha):

This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have...   More...
Antigene in dieser Kategorie:
NFKBIB (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, beta): NFKBIB Antikörper NFKBIB ELISA Kits NFKBIB Proteine
NFKBIE (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, epsilon): NFKBIE Antikörper NFKBIE ELISA Kits NFKBIE Proteine
NFKBIZ (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, zeta): NFKBIZ Antikörper NFKBIZ ELISA Kits NFKBIZ Proteine

Kinasen

IRAK1 (Interleukin-1 Receptor-Associated Kinase 1):

This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene....   More...

RIPK1 (Receptor (TNFRSF)-Interacting serine-threonine Kinase 1):

Serine-threonine kinase which transduces inflammatory and cell-death signals (necroptosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication...   More...
Antigene in dieser Kategorie:
IRAK4 (Interleukin-1 Receptor-Associated Kinase 4): IRAK4 Antikörper IRAK4 ELISA Kits IRAK4 Proteine
MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7): MAP3K7 Antikörper MAP3K7 ELISA Kits MAP3K7 Proteine
PRKACA (Protein Kinase A, alpha): PRKACA Antikörper PRKACA ELISA Kits PRKACA Proteine
PRKCZ - PKC zeta: PRKCZ Antikörper PRKCZ ELISA Kits PRKCZ Proteine

Proteinkinasen

CHUK (conserved Helix-Loop-Helix Ubiquitous Kinase):

This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor. [provided by RefSeq, Jul 2008].   More...

IKBKG (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase gamma):

This gene encodes the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, which activates NF-kappaB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Mutations in this gene result in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. Multiple transcript variants encoding...   More...
Antigene in dieser Kategorie:
IKBKB (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase beta): IKBKB Antikörper IKBKB ELISA Kits IKBKB Proteine
MAP3K14 (Mitogen-Activated Protein Kinase Kinase Kinase 14): MAP3K14 Antikörper MAP3K14 ELISA Kits MAP3K14 Proteine

Rezeptoren

EGFR (Epidermal Growth Factor Receptor):

The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation....   More...

IL1R1 (Interleukin 1 Receptor, Type I):

The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This protein is a receptor for interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA). It is an important mediator involved in many cytokine induced immune and inflammatory responses. This gene along with interleukin 1 receptor, type II (IL1R2),...   More...

TNFRSF1A (Tumor Necrosis Factor Receptor Superfamily, Member 1A):

The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is one of the major receptors for the tumor necrosis factor-alpha. This receptor can activate NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this...   More...
Antigene in dieser Kategorie:
CD40 (CD40 Molecule, TNF Receptor Superfamily Member 5): CD40 Antikörper CD40 ELISA Kits CD40 Proteine
GHR - Growth Hormone Receptor: GHR Antikörper GHR ELISA Kits GHR Proteine
INSR - Insulin Receptor: INSR Antikörper INSR ELISA Kits INSR Proteine
ITGB2 - Integrin beta 2: ITGB2 Antikörper ITGB2 ELISA Kits ITGB2 Proteine
IL1RAP (Interleukin 1 Receptor Accessory Protein): IL1RAP Antikörper IL1RAP ELISA Kits IL1RAP Proteine
IL1R2 (Interleukin 1 Receptor, Type II): IL1R2 Antikörper IL1R2 ELISA Kits IL1R2 Proteine
IL-1R1 - IL1R1: IL-1R1 Antikörper IL-1R1 ELISA Kits  
LTBR (Lymphotoxin beta Receptor (TNFR Superfamily, Member 3)): LTBR Antikörper LTBR ELISA Kits LTBR Proteine
NGFR (Nerve Growth Factor Receptor): NGFR Antikörper NGFR ELISA Kits NGFR Proteine
CD265 - RANK: CD265 Antikörper CD265 ELISA Kits CD265 Proteine
TNFRSF11A (Tumor Necrosis Factor Receptor Superfamily, Member 11a, NFKB Activator): TNFRSF11A Antikörper TNFRSF11A ELISA Kits TNFRSF11A Proteine
TNFRSF13C (Tumor Necrosis Factor Receptor Superfamily, Member 13C): TNFRSF13C Antikörper TNFRSF13C ELISA Kits TNFRSF13C Proteine
TNFRSF1B (Tumor Necrosis Factor Receptor Superfamily, Member 1B): TNFRSF1B Antikörper TNFRSF1B ELISA Kits TNFRSF1B Proteine

Transcriptionsfaktoren

NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1):

This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as...   More...

RELB - V-Rel Reticuloendotheliosis Viral Oncogene Homolog B

NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers...   More...
Antigene in dieser Kategorie:
NFKB2 - Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 2: NFKB2 Antikörper NFKB2 ELISA Kits  
NFkBP65 - p65: NFkBP65 Antikörper NFkBP65 ELISA Kits NFkBP65 Proteine