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Immunology/Inflammation(免疫及炎症)

The immune and inflammation-related pathway including the Toll-like receptors pathway, the B cell receptor signaling pathway, the T cell receptor signaling pathway, etc.

Toll-like receptors (TLRs) play a central role in host cell recognition and responses to microbial pathogens. TLR4 initially recruits TIRAP and MyD88. MyD88 then recruits IRAKs, TRAF6, and the TAK1 complex, leading to early-stage activation of NF-κB and MAP kinases [1]. TLR4 is endocytosed and delivered to intracellular vesicles and forms a complex with TRAM and TRIF, which then recruits TRAF3 and the protein kinases TBK1 and IKKi. TBK1 and IKKi catalyze the phosphorylation of IRF3, leading to the expression of type I IFN [2].

BCR signaling is initiated through ligation of mIg under conditions that induce phosphorylation of the ITAMs in CD79, leading to the activation of Syk. Once Syk is activated, the BCR signal is transmitted via a series of proteins associated with the adaptor protein B-cell linker (Blnk, SLP-65). Blnk binds CD79a via non-ITAM tyrosines and is phosphorylated by Syk. Phospho-Blnk acts as a scaffold for the assembly of the other components, including Bruton’s tyrosine kinase (Btk), Vav 1, and phospholipase C-gamma 2 (PLCγ2) [3]. Following the assembly of the BCR-signalosome, GRB2 binds and activates the Ras-guanine exchange factor SOS, which in turn activates the small GTPase RAS. The original RAS signal is transmitted and amplified through the mitogen-activated protein kinase (MAPK) pathway, which including the serine/threonine-specific protein kinase RAF followed by MEK and extracellular signal related kinases ERK 1 and 2 [4]. After stimulation of BCR, CD19 is phosphorylated by Lyn. Phosphorylated CD19 activates PI3K by binding to the p85 subunit of PI3K and produce phosphatidylinositol-3,4,5-trisphosphate (PIP3) from PIP2, and PIP3 transmits signals downstream [5].

Central process of T cells responding to specific antigens is the binding of the T-cell receptor (TCR) to specific peptides bound to the major histocompatibility complex which expressed on antigen-presenting cells (APCs). Once TCR connected with its ligand, the ζ-chain–associated protein kinase 70 molecules (Zap-70) are recruited to the TCR-CD3 site and activated, resulting in an initiation of several signaling cascades. Once stimulation, Zap-70 forms complexes with several molecules including SLP-76; and a sequential protein kinase cascade is initiated, consisting of MAP kinase kinase kinase (MAP3K), MAP kinase kinase (MAPKK), and MAP kinase (MAPK) [6]. Two MAPK kinases, MKK4 and MKK7, have been reported to be the primary activators of JNK. MKK3, MKK4, and MKK6 are activators of P38 MAP kinase [7]. MAP kinase pathways are major pathways induced by TCR stimulation, and they play a key role in T-cell responses.

Phosphoinositide 3-kinase (PI3K) binds to the cytosolic domain of CD28, leading to conversion of PIP2 to PIP3, activation of PKB (Akt) and phosphoinositide-dependent kinase 1 (PDK1), and subsequent signaling transduction [8].

 

References

[1] Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors[J]. Nature immunology, 2010, 11(5): 373-384.

[2] Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity[J]. Immunity, 2011, 34(5): 637-650.

[3] Packard T A, Cambier J C. B lymphocyte antigen receptor signaling: initiation, amplification, and regulation[J]. F1000Prime Rep, 2013, 5(40.10): 12703.

[4] Zhong Y, Byrd J C, Dubovsky J A. The B-cell receptor pathway: a critical component of healthy and malignant immune biology[C]//Seminars in hematology. WB Saunders, 2014, 51(3): 206-218.

[5] Baba Y, Matsumoto M, Kurosaki T. Calcium signaling in B cells: regulation of cytosolic Ca 2+ increase and its sensor molecules, STIM1 and STIM2[J]. Molecular immunology, 2014, 62(2): 339-343.

[6] Adachi K, Davis M M. T-cell receptor ligation induces distinct signaling pathways in naive vs. antigen-experienced T cells[J]. Proceedings of the National Academy of Sciences, 2011, 108(4): 1549-1554.

[7] Rincón M, Flavell R A, Davis R A. The Jnk and P38 MAP kinase signaling pathways in T cell–mediated immune responses[J]. Free Radical Biology and Medicine, 2000, 28(9): 1328-1337.

[8] Bashour K T, Gondarenko A, Chen H, et al. CD28 and CD3 have complementary roles in T-cell traction forces[J]. Proceedings of the National Academy of Sciences, 2014, 111(6): 2241-2246.

Products for  Immunology/Inflammation

  1. Cat.No. 产品名称 Information
  2. GC91820 PDIC-NS PDIC-NS is an activator of stimulator of interferon genes (STING).
  3. GC91805 DB2313 (hydrochloride) DB2313 is an inhibitor of the transcription factor PU.
  4. GC91789 LB244 LB244 is an irreversible STING antagonist.
  5. GC91783 FA16 FA16 is a ferroptosis inducer and an inhibitor of the system xc- cystine/glutamate transporter.
  6. GC91777 NVS-STG2 NVS-STG2 is an agonist of stimulator of interferon genes (STING).
  7. GC91776 PD-1/PD-L1 Inhibitor N11

    PD-1/PD-L1 Interaction Inhibitor,Programmed Cell Death 1/Programmed Cell Death-Ligand 1 Inhibitor N11

    PD-1/PD-L1 inhibitor N11 is an inhibitor of the protein-protein interaction between programmed cell death protein 1 (PD-1) and PD-1 ligand (PD-L1; IC50 = 6.3 nM).
  8. GC91768 GSK205 (hydrobromide) GSK205 is an inhibitor of transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential ankyrin 1 (TRPA1; IC50s = 4.19 and 5.56 µM, respectively, for the rat channels).
  9. GC91690 TASP0277308 TASP0277308 is a sphingosine-1-phosphate receptor 1 (S1P1) antagonist (IC50 = 4.2 nM).
  10. GC91688 PDIC-NN PDIC-NN is an intermediate in the synthesis of PDIC-NS , an activator of stimulator of interferon genes (STING) with anticancer activity.
  11. GC91681 Loxoprofen-SRS Loxoprofen-SRS is a non-steroidal anti-inflammatory drug (NSAID) and COX inhibitor (IC50s = 0.5 and 0.39 for recombinant human COX-1 and COX-2, respectively) and an active metabolite of the prodrug loxoprofen .
  12. GC91680 4-Acetamido Antipyrine

    4-AAAP,NSC 331807

    4-Acetamido antipyrine (4-AAAP) is an active metabolite of the non-opioid analgesic and antipyretic prodrug metamizole .
  13. GC91673 CPPD-Q

    CPPD-quinone

    CPPD-Q is a p-phenylenediamine quinone (PPD-Q) and an oxidized derivative of the antiozonant CPPD.
  14. GC91670 MRSA Antibiotic 1 MRSA antibiotic 1 is an antibiotic.
  15. GC91659 BDW-OH BDW-OH is an active metabolite of the STING agonist and prodrug BDW568 .
  16. GC91623 Ferroptosis Inducer 24 Ferroptosis inducer 24 is an inducer of ferroptosis.
  17. GC91612 FDW028 FDW028 is an inhibitor of fucosyltransferase 8 (FUC8).
  18. GC91598 GPX4 16

    Glutathione Peroxidase 4 16

    GPX4 16 is an inhibitor of glutathione peroxidase 4 (GPX4).
  19. GC91595 PDIC-NC PDIC-NC is an activator of stimulator of interferon genes (STING) and an anticancer agent.
  20. GC91590 DTPD-Q

    2,5-Bis(o-tolylamino)cyclohexa-2,5-diene-1,4-dione,DTPD-quinone

    DTPD-Q is an oxidized derivative of the antioxidant and methylphenyl substituted p-phenylenediamine DTPD.
  21. GC26431 Pentacosafluorotridecanoic Acid

    全氟十三烷酸,PFTrDA

    Perfluorotridecanoic Acid (Perfluorinated Compound (PFC)) is a perfluorinated alkyl acid (PFAA) and a possible organic pollutant.

  22. GC72610 Cartap hydrochloride Cartap hydrochloride一种有机氮杀虫剂,可在分离的小鼠和兔膈神经膈肌中引起明显的不可逆钙依赖性挛缩。
  23. GC72575 L-Glutamic acid monosodium (hydrate) L-Glutamic acid monosodium (hydrate)是一种营养添加剂和调味剂。
  24. GC72574 2-Oxopropanoate-13C5 sodium 2-Oxopropanoate-13C5 sodium是13C标记的2-氧丙酸钠。
  25. GC72573 Sodium 2-oxopropanoate-13C Sodium 2-oxopropanoate-13C是13C标记的2-氧丙酸钠。
  26. GC72511 L-Cystathionine dihydrochloride L-Cystathionine dihydrochloride是一种非蛋白硫醚,是与含硫氨基酸代谢状态相关的关键氨基酸。
  27. GC72473 Crovalimab Crovalimab(SKY59;RO7112689)是一种新型的人源化C5抗体,具有pH依赖性,在pH 7.4和5.8时的KD分别为15.2 nM和16.8μM。
  28. GC72471 Remtolumab Remtolumab (ABT-122)是一种双变量结构域免疫球蛋白,可中和肿瘤坏死因子α (TNFα)和IL-17A。
  29. GC72456 Eblasakimab Eblasakimab (ASLAN004;CSL-334)是一种特异性靶向IL13RA1的人IgG4抗体,主要由CHO-K1细胞表达。
  30. GC72433 Nemvaleukin alfa Nemvaleukin alfa (ALKS 4230)是一种IL-2融合蛋白,可选择性结合中等亲和力的IL-2R。
  31. GC72429 Mirikizumab Mirikizumab(LY3074828)是一种人源化IgG4单克隆抗体,靶向白细胞介素23的p19亚基。
  32. GC72428 Melrilimab Melrilimab(GSK 3772847)是一种IgG2κ抗IL1RL1/ST2/IL33R/DER4/FIT-1单克隆抗体。
  33. GC72426 Manfidokimab Manfidokimab (AK120)是一种抗白细胞介素4受体α (IL-4Rα) IgG4单克隆抗体。
  34. GC72424 Lutikizumab Lutikizumab (ABT-981)是一种抗il -1α和IL-1β双可变结构域免疫球蛋白。
  35. GC72418 Inolimomab Inolimomab是一种抗白细胞介素-2受体(IL-2R) α链单克隆抗体。
  36. GC72415 Goflikicept Goflikicept(RPH 104)是一种杂交蛋白,可选择性结合并灭活循环中的IL-1β和IL-1α。
  37. GC72397 Ziltivekimab Ziltivekimab(COR-001)是一种有效降低血清CRP的人抗IL-6单克隆抗体。
  38. GC72396 Cendakimab Cendakimab(RPC4046;ABT 308;CC-93538)是一种针对IL-13分子的选择性人源化重组单克隆抗体。
  39. GC72391 Avdoralimab Avdoralimab(IPH 5401)是一种全人IgGκ单克隆抗体,靶向补体C5a受体1(C5aR1),阻止其与C5a结合。
  40. GC72390 Anrukinzumab Anrukinzumab(IMA-638)是一种人源化的抗IL-13单克隆抗体。
  41. GC72381 Sonelokimab Sonelokimab(ALX 0761;M 1095)是一种三价纳米体,由单价骆驼科动物衍生的纳米体组成,对人白细胞介素(IL)-17A、IL-17F和人血清白蛋白VHH具有特异性。
  42. GC72380 Vobarilizumab Vobarilizumab(ALX-0061)是一种抗IL-6R单克隆抗体(mAb)(Kd:0.19 pM)。
  43. GC72378 Neihulizumab Neihulizumab(ALTB-168)是一种免疫检查点激动性抗体,与人CD162(PSGL-1)结合,导致活化T细胞下调。
  44. GC72367 Vunakizumab Vunakizumab(抗人IL17A重组抗体)是一种重组人IgGκ单克隆抗体,靶向IL-17A并抑制其与IL-17受体的相互作用。
  45. GC72365 Visilizumab Visilizumab(抗人CD3E重组抗体)是一种人源化低Fc受体结合的抗CD3单克隆IgG2抗体。
  46. GC72363 Timolumab Timolumab(BTT1023),一种特异性结合VAP-1的重组全人单克隆抗体。
  47. GC72359 Quilizumab Quilizumab(抗人NGcGM3重组抗体)是一种人源化IgG1κ单克隆抗体。
  48. GC72358 Perakizumab Perakizumab (RG4934)是一种人源化抗IL-17A (Interleukin Related)的IgG1κ单克隆抗体。
  49. GC72354 Lampalizumab Lampalizumab (RG 7417)是一种人源化单克隆抗体,靶向补体因子D的替代补体途径。
  50. GC72352 Fontolizumab Fontolizumab(HuZAF)是一种人源化单克隆抗IFN-γ抗体。
  51. GC72345 Tildrakizumab Tildrakizumab(SCH 900222)是一种人源化抗IL-23(p19亚基)单克隆抗体。

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