Toll样受体信号通路

作为机体的第一道防线,天然免疫系统是通过模式识别受体(Pattern Recognition Receptors , PRRs)或信号感受器识别病原体相关分子模式(Pathogen-associated Molecular Patterns, PAMPs)和内源性损伤相关分子模式(Damage-associated Molecular Patterns, DAMPs)而被启动的 [1]。 其中,Toll样受体(Toll-like Receptors,TLRs)因与果蝇中Toll蛋白结构相似而得名,是最早被鉴定并在从昆虫到人类的多种动物中被广泛研究的模式识别受体[2]。
TLRs在包括免疫细胞和非免疫细胞的多种细胞类型上表达,它们是跨膜受体,可以定位于细胞表面或内体[3]。他们被外源性和可能的内源性配体结合,在连接天然免疫和炎症的各种免疫细胞中触发促炎信号级联。 结合配体后,形成TLR同源或异源二聚体,并通过MyD88、TIRAP、TRAM和/或TRIF等不同接头蛋白激活MyD88依赖和/或MyD88非依赖的信号途径[4]。除TLR3外,所有的TLRs都可以通过MyD88介导下游信号,而TLR3信号通过TRIF介导下游信号。然而,TLR2和TLR4需要通过TIRAP招募MyD88。TLR4比较特别,因为它可以同时利用MyD88和TRIF作为信号接头分子启动下游信号,但它还需要接头分子TRAM来招募TRIF和TIRAP来招募MyD88。在MyD88依赖的信号途径中,MyD88招募IRAK并造成这些IRAK被磷酸化,然后招募TRAF泛素连接酶。通常情况下,TRAF6与TAK和TAB形成复合物,TAK通过磷酸化修饰激活下游IKK-NF-κB和MAPK级联,进而导致转录因子NF-κB和AP-1的激活,并控制促炎细胞因子和其他免疫相关基因的表达[5]。也有报道发现,在特殊情况下TRAF6和MyD88可以通过激活IRF1或IRF5介导这个过程[6]。而TRAF3招募TBK1和IKKε,磷酸化和激活转录因子IRF(主要是IRF-3和IRF-7)并导致I型干扰素的产生。此外,在病毒感染时,TRAF6可以与IRF7、MyD88、IRAK4和IRAK1形成复合体[7]。 MyD88非依赖的信号途径存在于TLR3和TLR4下游,是由TRIF介导并通过RIPK1、TRAF6或TRAF3激活类似的下游信号[4]。
此外,TLRs与其他PRRs(如C型凝集素受体、NOD样受体和RIG-I样受体)的串话,使多种信号转导整合为一个网络,在感染和免疫中发挥协同作用[8]。TLRs还与PRRs以外的一些信号通路相互作用,例如,与低氧依赖通路共同参与肿瘤微环境中代谢重新编程的调控[9],与NRF2通路[10]和PPARs[11]共同参与炎症调节。

ABclonal针对Toll样受体信号通路研究,提供以下常见核心靶点的产品

TLR4 Rabbit pAb

Phospho-c-Jun-S73 Rabbit pAb

IRAK4 Rabbit pAb

IRF3 Rabbit pAb

TBK1/NAK Rabbit mAb

Phospho-TBK1/NAK-S172 Rabbit mAb

IKKβ Rabbit mAb

Phospho-JNK1/2/3-T183/T183/T221 Rabbit mAb

TLR信号通路精选研究产品

分类
研究靶点 产品货号 产品名称 应用 物种
TLR家族成员
TLR1A0997TLR1 Rabbit pAbELISA,WB,IHC-P,IF/ICCHuman, Mouse, Rat
TLR2A19125TLR2 Rabbit mAbELISA,WB,IF/ICCHuman
TLR3A11778TLR3 Rabbit pAbELISA,WB,IHC-P,IF/ICCHuman, Mouse, Rat
TLR4A5258TLR4 Rabbit pAbELISA,WB,IF/ICCHuman, Mouse, Rat
TLR5A8765TLR5 Rabbit mAbELISA,WBHuman, Mouse
TLR6A8185TLR6 Rabbit pAbELISA,WB,IF/ICCHuman, Mouse
TLR7A21973TLR7 Rabbit mAbELISA,WB,IHC-PMouse, Rat
TLR7A19126TLR7 Rabbit mAbELISA,WBHuman
TLR9A14642TLR9 Rabbit pAbELISA,WB,IHC-PHuman, Mouse, Rat
信号转导分子
MYD88A19082[KO Validated] MyD88 Rabbit mAbELISA,WB,IHC-PHuman, Mouse, Rat
MYD88A21905MyD88 Rabbit mAbELISA,WBMouse, Rat
TRAF3A3094TRAF3 Rabbit pAbELISA,WB,IHC-P,IF/ICCHuman, Mouse, Rat
TRAF6A16991TRAF6 Rabbit pAbELISA,WB,IF/ICCHuman, Mouse, Rat
IRAK1A4439IRAK1 Rabbit mAbELISA,WBHuman
IRAK2A4655IRAK2 Rabbit mAbELISA,WB,IHC-PHuman, Rat
IRAK4A6208IRAK4 Rabbit pAbELISA,WB,IHC-P,IF/ICCHuman, Mouse, Rat
MAP3K7A19077TAK1 Rabbit mAbELISA,WB,IPHuman, Mouse
MAP3K7A9437Phospho-TAK1-S439 Rabbit mAbELISA,WBMouse
TBK1A3458TBK1/NAK Rabbit mAbELISA,WB,IF/ICC,IPHuman, Mouse, Rat
TBK1AP1026Phospho-TBK1/NAK-S172 Rabbit mAbELISA,WBHuman, Mouse
CHUKA19694IKKα Rabbit mAbELISA,WBHuman, Mouse
IKBKBA19606IKKβ Rabbit mAbELISA,IF/ICCHuman, Mouse, Rat
CHUK/IKBKBAP0546Phospho-IKKα/β-S176/180 Rabbit pAbELISA,WB,IHC-PHuman, Mouse, Rat
IKBKEA3463IKKε Rabbit mAbELISA,WB,IHC-PHuman, Mouse, Rat
MAPK14A4771[KO Validated] p38 MAPK Rabbit mAbELISA,WBHuman, Mouse, Rat
MAPK14A5049p38 MAPK Rabbit mAbELISA,WB,IF/ICCHuman, Mouse, Rat
MAPK14AP1311Phospho-p38 MAPK-T180/Y182 Rabbit mAbELISA,WBHuman, Mouse, Rat
MAPK14AP0526Phospho-p38 MAPK-T180/Y182 Rabbit pAbELISA,WB,IF/ICCHuman, Mouse, Rat
MAPK8/MAPK9/MAPK10A4867JNK1/2/3 Rabbit mAbELISA,WB,IF/ICCHuman, Mouse, Rat
MAPK8/MAPK9AP0473Phospho-JNK1/2-T183/Y185 Rabbit pAbELISA,WBHuman, Mouse, Rat
MAPK8/MAPK9/MAPK10AP0631Phospho-JNK1/2/3-T183/T183/T221 Rabbit mAbELISA,WB,IHC-P,IF/ICCHuman, Mouse, Rat
转录因子
RELAA19653NF-kB p65/RelA Rabbit mAbELISA,WB,IHC-P,IF/ICC,ChIPHuman, Mouse, Rat, Monkey
RELAAP1294Phospho-NF-kB p65/RelA-S536 Rabbit mAbELISA,WBHuman,Mouse,Rat
RELAAP0124Phospho-NF-kB p65/RelA-S536 Rabbit pAbELISA,WB,IF/ICCHuman, Mouse, Rat
JUNA11378c-Jun Rabbit pAbELISA,WBHuman, Mouse, Rat
JUNAP0105Phospho-c-Jun-S63 Rabbit mAbELISA,WB,IF/ICCHuman, Mouse, Rat
JUNAP0119Phospho-c-Jun-S73 Rabbit pAbELISA,WB,IHC-PHuman, Mouse, Rat
JUNAP1003Phospho-c-Jun-T91 Rabbit mAbELISA,WB,IHC-PHuman, Mouse, Rat
IRF1A7692IRF1 Rabbit pAbELISA,WB,IHC-P,IF/ICCHuman, Mouse, Rat
IRF3A11118IRF3 Rabbit pAbELISA,WB,IHC-P,IF/ICC,ChIP,IPHuman, Mouse, Rat
IRF3A19717[KO Validated] IRF3 Rabbit mAbELISA,WBHuman, Mouse
IRF3AP0995Phospho-IRF3-S386 Rabbit mAbELISA,WBHuman
IRF3AP0623Phospho-IRF3-S396 Rabbit pAbELISA,WB,IHC-PHuman, Mouse, Rat
IRF5A11106IRF5 Rabbit mAbELISA,WB,IPHuman, Mouse
IRF7A0159IRF7 Rabbit pAbELISA,WBMouse
  • 缩略语注释:
  • RIG-I, retinoic acid-inducible gene
  • MAVS,mitochondrial antiviral signaling
  • MDA5, melanoma differentiation associated gene 5
  • LGP2, laboratory of genetics and physiology 2
  • PAMP, pathogen-associated molecular patterns
  • pDCs, plasmacytoid dendritic cells
  • TRAF,TNF-receptor-associated factor
  • CARD9,caspase recruitment domain family member 9
  • TRADD, tumor necrosis factor receptor type 1-associated death domain
  • cIAP1/2, cellular inhibitor of apoptosis 1 and 2
  • TANK, TRAF Family Member Associated NFKB Activator
  • NAP1, NAK-associated protein 1
  • Tbkbp1, TBK1 binding protein 1
  • TAK,TGF-beta activated kinase
  • TAB, TAK1-associated binding protein 2
  • TBK, TANK binding kinase
  • IKK, inhibitor of nuclear factor kappa B kinase
  • RIPK1, receptor-interacting serine/threonine-protein kinase 1
  • FADD, Fas-associated protein with death domain
  • IRF, interferon regulatory factor
  • PCBP, poly(RC)-binding protein
  • Smurf2, smad ubiquitin regulatory factor 2
  • 参考文献:
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  • 5.J Mol Biol. (2013) 425(24):5009-5019.
  • 6.J Mol Signal. (2013) 8: 7.
  • 7.Eur J Immunol. (2017) 47(4):615-628.
  • 8.Trends Immunol. (2017) 38(3): 194-205.
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