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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. GC41875 11(Z),14(Z)-Eicosadienoic Acid methyl ester

    (11Z,14Z)-11,14-二十碳二烯酸甲酯

    A more lipid soluble form of 11(Z),14(Z)-eicosadienoic acid
  3. GC41868 10-Nitrooleate

    10-硝基油酸,CXA-10

    A novel endogenous lipid signalling molecule
  4. GC41866 10-methyl-9-(phenoxycarbonyl) Acridinium (trifluoromethylsulfonate)

    9-[(苯氧基)羰基]-10甲基三氟甲酰胺磺酸盐

    A chemiluminescent acridinium ester
  5. GC41865 10'-Desmethoxystreptonigrin

    10-去甲氧基链黑霉素

    An antibiotic
  6. GC41855 1,3-Distearoyl-2-Oleoyl-rac-glycerol

    1,3-Distearin-2-Olein, TG(18:0/18:1/18:0)

    A triacylglycerol
  7. GC41837 1,3,7-Trimethyluric Acid

    1,3,7-三甲基尿酸,8-oxo Caffeine, NSC 11259

    A metabolite of caffeine
  8. GC41742 (Z-IETD)2-Rh 110 (trifluoroacetate salt)

    (Z-Ile-Glu-Thr-Asp)2-R110, Rhodamine 110 bis-(N-CBZ-IETD)2

    A fluorogenic substrate for caspase-8
  9. GC41740 (S)-p38 MAPK Inhibitor III

    (S)-p38 MAP Kinase Inhibitor III, (S)-p38 Mitogen-activated Protein Kinase Inhibitor III

    A cell-permeable p38 MAP kinase inhibitor
  10. GC41721 (R)-α-Lipoic Acid

    硫辛酸; (R)-(+)-α-Lipoic acid; R-(+)-Thioctic acid

    A cyclic disulfide antioxidant
  11. GC41717 (R)-Gyramide A (hydrochloride)

    (R)-534F6

    A bacterial DNA gyrase inhibitor
  12. GC41712 (R)-3-hydroxy Myristic Acid

    3-羟基肉豆蔻酸

    A component of lipid A
  13. GC41703 (E)-C-HDMAPP (ammonium salt)

    (E)5hydroxy4methylpent3enyl pyrophosphate

    Activator of γδ-T-lymphocytes
  14. GC41702 (E)-5-(2-Bromovinyl)uracil

    (E)-5-(2-溴乙烯基)-2-脱氧尿苷

    A pyrimidine base
  15. GC41700 (E)-2-(2-Chlorostyryl)-3,5,6-trimethylpyrazine

    CSTMP

    A stilbene derivative with antioxidant and anticancer activities
  16. GC41698 (D)2-Rh 110 (trifluoroacetate salt)

    D2R, (Asp)2-Rhodamine 110, Rhodamine 110 bis-(L-aspartic acid amide)

    A fluorogenic caspase substrate
  17. GC41697 (Ala1)-PAR4 (1-6) amide (mouse) (trifluoroacetate salt)

    AY-NH2, AYPGKF-NH2, H-Ala-Tyr-Pro-Gly-Lys-Phe-NH2, PAR4-AP, Proteinase-Activated Receptor 4 Activating Peptide

    A peptide agonist of PAR4
  18. GC41655 (±)19(20)-EDP Ethanolamide

    19,20-DHEA epoxide, 19,20-epoxy Docosapentaenoic Acid Ethanolamide, 19,20-EDP-EA, 19,20-EDP epoxide

    An ω-3 endocannabinoid epoxide and CB receptor agonist
  19. GC41640 Asterriquinol D dimethyl ether A fungal metabolite
  20. GC41638 TSI-01 TSI-01是溶血磷脂酰胆碱酰基转移酶2(LPCAT2)的选择性抑制剂,对人 LPCAT2和LPCAT1的IC50值分别为0.47和3.02µM。
  21. GC41630 H2S Donor 5a

    N-(苯甲酰基硫基)苯甲酰胺,N-(Benzoylthio)benzamide

    H2S(硫化氢)供体 5a 作为稳定的半胱氨酸活化硫化氢供体,可以与半胱氨酸和还原型谷胱甘肽等含有巯基的还原剂反应,释放出 H2S。
  22. GC41627 Kumbicin C A fungal metabolite
  23. GC41626 Sappanone A Sappanone A是一种具有较强抗氧化和抗炎活性的同型异黄酮。
  24. GC41623 β-Elemonic Acid

    β-岚香酮酸

    A triterpene with anticancer activity
  25. GC41620 (R)-(-)-Mellein

    (R)-蜂蜜曲菌素,以及(S)-蜂蜜曲菌素,(R)-Mellein

    A dihydroisocoumarin compound with antibacterial, antimalarial, antifungal , and anticancer effects
  26. GC41617 (±)-α-Tocopherol

    β-生育酚

    A biologically active form of vitamin E
  27. GC41616 Methylcardol triene A phenol from cashew nut shell liquid
  28. GC41612 2'-O-Methylguanosine

    2'-甲氧基鸟苷

    A modified nucleoside
  29. GC41609 trans-Urocanic Acid

    尿刊酸,(E)-Urocanic acid; trans-UCA

    A major epidermal chromophore
  30. GC41601 CAY10591

    SIRT1 Activator 3, Sirtuin 1 Activator 3

    A SIRT1 activator
  31. GC41598 Tyrocidine Complex An antibiotic complex
  32. GC41595 Matairesinol

    罗汉松脂素

    A lignan with diverse biological activities
  33. GC41587 cis-Vaccenic Acid

    顺-十八碳烯酸

    An ω-7 fatty acid
  34. GC41584 Penicolinate A

    Penicolinate B dimethyl ester

    A fungal metabolite with diverse biological activities
  35. GC41583 BCN-E-BCN A probe for sulfenylated proteins
  36. GC41575 N-3-hydroxyoctanoyl-L-Homoserine lactone

    OHC8HSL

    A C8 quorum-sensing lactone
  37. GC41573 Theaflavin 3,3'-digallate

    茶黄素-3,3'-双没食子酸; TF-3; ZP10

    Theaflavin 3,3'-digallate(茶黄素-3,3'-双没食子酸; TF-3; ZP10)是一种有效的寨卡病毒(ZIKV)蛋白酶抑制剂,IC50值为2.3μM。
  38. GC41569 tetranor-PGDM lactone

    tetranorProstaglandin D Metabolite lactone

    A potential metabolite of PGD2
  39. GC41568 tetranor-PGAM

    tetranorProstaglandin A Metabolite

    A dehydration product of tetranor-PGEM
  40. GC41566 Malioxamycin

    An antibiotic

  41. GC41563 Globosuxanthone A A fungal metabolite
  42. GC41555 Cyclo(L-Phe-L-Val)

    DKP101516

    A bacterial metabolite
  43. GC41533 Silybin

    水飞蓟宾

    Hepatoprotective flavonoid and 5-LO inhibitor
  44. GC41531 Anacardic Acid Triene

    Anacardic Acid 15:3

    A polyunsaturated form of anacardic acid
  45. GC41520 Lachnone A A fungal metabolite
  46. GC41517 Linoleic Acid ethyl ester

    亚油酸乙酯,Linoleic Acid ethyl ester

    An esterified form of linoleic acid
  47. GC41502 β-Myrcene

    月桂烯; β-Myrcene

    A terpene with antioxidative properties
  48. GC41499 α-Phellandrene

    水芹烯

    A monoterpene with diverse biological activities
  49. GC41490 Aureusimine B

    Phevalin

    A natural pyrazinone
  50. GC41471 6-deoxy-L-Talose

    6-脱氧-L-塔罗糖

    A microbial monosaccharide
  51. GC41467 Reveromycin D

    雷弗霉素D

    A bacterial metabolite

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