我们推荐在您的浏览器上开启Javascript，以获得最佳效果。

NF-kappaB Signaling

NF-kappaB (核因子活化B细胞轻链增强子)是一种同源或异源二聚体转录因子，在各种信号转导通路网络中处于中枢地位。诸如细胞因子、生长因子以及激素、感染、氧化应激、某些药物和化学物质等众多信号均被传输至NF-kappaB复合物，随后继续传递，从而影响从细胞存活、凋亡、增殖到免疫应答和炎症等多个过程。此外，与其他信号通路发生的串扰也比较严重，如MAPK信号和p53通路。因此，它们极具多效性，即会影响大量表型性状。

NF-kappaB是一种存在于哺乳动物中的同源或异二聚体复合物，由RelA/p65、RelB、c-Rel、NFKB1/p105/p50和NFKB2/p100/p52等含Rel同源结构域(RHD)的蛋白构成。经典通路的异源二聚体RELA/p50复合物是其中含量最丰富的部分。所有NF-kB蛋白均具有N末端RHD，后者作为二聚化介质可以使前者结合至IkappaB抑制子，在DNA结合中发挥着必不可少的作用。然而，NF-kappaB蛋白却可以通过其C末端进行区分：RELA、RELB和c-Rel 包含的I类蛋白的特征在于其反式激活结构域，而 II类蛋白NFKB1/p105/p50和NFKB2/p100/p52则具有锚蛋白重复转录抑制结构域。在经典通路中，通过与抑制IkappaB蛋白的相互作用，NF-kappaB在细胞质中处于非激活状态。在上述任一刺激引发的NF-kappaB信号传导刺激下，这些调节因子被由蛋白激酶IKKalpha、IKKbeta和NEMO构成的IKK激酶复合物磷酸化。磷酸化为蛋白酶体降解标志IkappaB抑制子，从而将NF-kappaB转为游离状态。一旦转入游离状态，NF-kB将被翻译后的修饰进一步活化并转运至它与特异kappaB元素交互作用的细胞核内。

根据细胞类型和接收到的刺激性质，非经典通路也可以使用。该通路的核心调节子为NF-kappaB诱导激酶(NIK)，它可以激活IKKalpha，从而导致P100的磷酸化。p100然后被处理为p52蛋白，由此促使p52/RelB NF-kappaB 二聚体发生激活和核移位，并诱导靶向基因的表达。经典通路并不依赖蛋白质合成，并且会对众多刺激迅速作出响应，从而促成各种各样的下游效应。与此相反，非经典通路则较为缓慢和持久，且只会对信号的某一子集作出响应，从而产生某些更具特异性的效应。

References

Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 2013 Aug 2;12:86. doi: 10.1186/1476-4598-12-86. PMID: 23915189; PMCID: PMC3750319.
Oeckinghaus A, Hayden MS, Ghosh S. Crosstalk in NF-κB signaling pathways. Nat Immunol. 2011 Jul 19;12(8):695-708. doi: 10.1038/ni.2065. PMID: 21772278.
Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a000034. doi: 10.1101/cshperspect.a000034. PMID: 20066092; PMCID: PMC2773619.
Israël A. The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harb Perspect Biol. 2010 Mar;2(3):a000158. doi: 10.1101/cshperspect.a000158. PMID: 20300203; PMCID: PMC2829958.
King CC, Sastri M, Chang P, Pennypacker J, Taylor SS. The rate of NF-κB nuclear translocation is regulated by PKA and A kinase interacting protein 1. PLoS One. 2011 Apr 27;6(4):e18713. doi: 10.1371/journal.pone.0018713. PMID: 21556136; PMCID: PMC3083391.
Sun SC. Non-canonical NF-κB signaling pathway. Cell Res. 2011 Jan;21(1):71-85. doi: 10.1038/cr.2010.177. Epub 2010 Dec 21. PMID: 21173796; PMCID: PMC3193406.

Adaptors

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

TRADD (TNFRSF1A-Associated Via Death Domain):

KHDRBS1 (KH Domain Containing, RNA Binding, Signal Transduction Associated 1):

SQSTM1 (Sequestosome 1):

SLC39A3 (Solute Carrier Family 39 (Zinc Transporter), Member 3):

SLC39A3 抗体

Cytokines

IL1A (Interleukin 1 alpha):

TNF alpha (Tumor Necrosis Factor alpha):

CD40LG - CD40 Ligand:

IL1RN (Interleukin 1 Receptor Antagonist):

IL1B - IL-1 beta:

LTB (Lymphotoxin beta (TNF Superfamily, Member 3)):

TNFSF11 - RANKL:

TNFSF13B - BAFF:

Enzymes

TRAF1 (TNF Receptor-Associated Factor 1):

TRAF2 (TNF Receptor-Associated Factor 2):

TRAF3 (TNF Receptor-Associated Factor 3):

TRAF5 (TNF Receptor-Associated Factor 5):

TRAF6 (TNF Receptor-Associated Factor 6):

Growth factors

EGF (Epidermal Growth Factor):

NGFB (Nerve Growth Factor beta):

GH1 - Growth Hormone 1:

GH2 - Growth Hormone 2:

INS - Insulin:

TGFA (Transforming Growth Factor, alpha):

Inhibitors

BCL3 (B-Cell CLL/lymphoma 3):

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

NFKBIB (NF-kappa-B inhibitor beta):

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

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

Kinases

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

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

IRAK4 (Interleukin-1 Receptor-Associated Kinase 4):

MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7):

PRKACA (Protein Kinase A, alpha):

PRKCZ - PKC zeta:

Protein kinases

CHUK - IKK alpha:

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

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

MAP3K14 (Mitogen-Activated Protein Kinase Kinase Kinase 14):

Receptors

EGFR (Epidermal Growth Factor Receptor):

IL1R1 (Interleukin 1 Receptor, Type I):

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

CD40 (CD40):

GHR - Growth Hormone Receptor:

INSR - Insulin Receptor:

ITGB2 - Integrin beta 2:

IL1RAP (Interleukin 1 Receptor Accessory Protein):

IL1R2 (Interleukin 1 Receptor, Type II):

IL1R1 (Interleukin 1 Receptor, Type I):

LTBR (Lymphotoxin beta Receptor (TNFR Superfamily, Member 3)):

NGFR (Nerve Growth Factor Receptor):

TNFRSF11A (Tumor Necrosis Factor Receptor Superfamily, Member 11a, NFKB Activator):

References

Adaptors

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

TRADD (TNFRSF1A-Associated Via Death Domain):

KHDRBS1 (KH Domain Containing, RNA Binding, Signal Transduction Associated 1):

SQSTM1 (Sequestosome 1):

SLC39A3 (Solute Carrier Family 39 (Zinc Transporter), Member 3):

Cytokines

IL1A (Interleukin 1 alpha):

TNF alpha (Tumor Necrosis Factor alpha):

CD40LG - CD40 Ligand:

IL1RN (Interleukin 1 Receptor Antagonist):

IL1B - IL-1 beta:

LTB (Lymphotoxin beta (TNF Superfamily, Member 3)):

TNFSF11 - RANKL:

TNFSF13B - BAFF:

Enzymes

TRAF1 (TNF Receptor-Associated Factor 1):

TRAF2 (TNF Receptor-Associated Factor 2):

TRAF3 (TNF Receptor-Associated Factor 3):

TRAF5 (TNF Receptor-Associated Factor 5):

TRAF6 (TNF Receptor-Associated Factor 6):

Growth factors

EGF (Epidermal Growth Factor):

NGFB (Nerve Growth Factor beta):

GH1 - Growth Hormone 1:

GH2 - Growth Hormone 2:

INS - Insulin:

TGFA (Transforming Growth Factor, alpha):

Inhibitors

BCL3 (B-Cell CLL/lymphoma 3):

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

NFKBIB (NF-kappa-B inhibitor beta):

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

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

Kinases

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

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

IRAK4 (Interleukin-1 Receptor-Associated Kinase 4):

MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7):

PRKACA (Protein Kinase A, alpha):

PRKCZ - PKC zeta:

Protein kinases

CHUK - IKK alpha:

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

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

MAP3K14 (Mitogen-Activated Protein Kinase Kinase Kinase 14):

Receptors

EGFR (Epidermal Growth Factor Receptor):

IL1R1 (Interleukin 1 Receptor, Type I):

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

CD40 (CD40):

GHR - Growth Hormone Receptor:

INSR - Insulin Receptor:

ITGB2 - Integrin beta 2:

IL1RAP (Interleukin 1 Receptor Accessory Protein):

IL1R2 (Interleukin 1 Receptor, Type II):

IL1R1 (Interleukin 1 Receptor, Type I):

LTBR (Lymphotoxin beta Receptor (TNFR Superfamily, Member 3)):

NGFR (Nerve Growth Factor Receptor):

TNFRSF11A (Tumor Necrosis Factor Receptor Superfamily, Member 11a, NFKB Activator):

TNFRSF13C (Tumor Necrosis Factor Receptor Superfamily, Member 13C):

TNFRSF1B (Tumor Necrosis Factor Receptor Superfamily, Member 1B):

Transcription factors

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

RELB (V-Rel Reticuloendotheliosis Viral Oncogene Homolog B):

NFkBP65 - NF-kB p65:

antibodies-online

genomics-online