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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. GC48911 Tubermycin B

    吩嗪-1-羧酸

    A bacterial metabolite with antifungal and fungicidal activities
  3. GC48910 2-Hydroxyanthraquinone

    2-羟基蒽醌

    An anthraquinone with antibacterial and estrogenic activities
  4. GC48908 Ornidazole-d5

    Ro 7-0207-d5

    An internal standard for the quantification of ornidazole
  5. GC48907 Metaxalone-d6

    AHR438-d6; NSC170959-d6

    An internal standard for the quantification of metaxalone
  6. GC48900 Isocurcumenol

    异莪术烯醇

    A sesquiterpene with diverse biological activities
  7. GC48896 Nitrofurantoin-13C3

    硝基呋喃妥因-13C3

    An internal standard for the quantification of nitrofurantoin
  8. GC48894 SIH

    2-异丙基噻吨酮

    An iron chelator
  9. GC48893 Carbazomycin B A bacterial metabolite with diverse biological activities
  10. GC48889 Methazolamide-d6

    L584601-d6

    An internal standard for the quantification of methazolamide
  11. GC48880 7-Methoxyflavone

    7-甲氧基黄酮

    A flavone with diverse biological activities
  12. GC48878 Carbazomycin A A bacterial metabolite with diverse biological activities
  13. GC48857 Methylchloroisothiazolinone/Methylisothiazolinone Mixture

    CMIT/MIT, MCI/MI, MCIT/MIT

    A mixture of isothiazolinone biocides
  14. GC48856 Fenspiride-d5

    Decaspiride-d5

    An internal standard for the quantification of fenspiride
  15. GC48853 Pirlindole-d4 (hydrochloride) An internal standard for the quantification of pirlindole
  16. GC48850 Carbazomycin C A bacterial metabolite with diverse biological activities
  17. GC48848 Albendazole-d7

    阿苯达唑-D7,SKF-62979-d7

    An internal standard for the quantification of albendazole
  18. GC48842 Actiphenol

    放线菌酚

    A bacterial metabolite with antiviral activity
  19. GC48841 Arbutin-d4

    β-Arbutin-d4

    An internal standard for the quantification of arbutin
  20. GC48839 Nifuroxazide-d4

    硝呋齐特 d4

    An internal standard for the quantification of nifuroxazide
  21. GC48837 NG,NG-dimethyl-L-Arginine-d6 (hydrochloride)

    NG,NG-Dimethylarginine-d6 dihydrochloride

    An internal standard for the quantification of NG,NG-dimethyl-L-arginine
  22. GC48827 Flufenamic Acid-d4

    FFA-d4, Fluphenamic Acid-d4

    An internal standard for the quantification of flufenamic acid
  23. GC48826 Carbazomycin D A bacterial metabolite with diverse biological activities
  24. GC48815 5,7,8-Trimethoxydictamnine

    Acronycidine, NSC 30619

    A quinoline alkaloid with antimalarial activity
  25. GC48805 Methapyrilene (hydrochloride)

    盐酸美沙吡林,Thenylpyramine hydrochloride

    An H1 receptor antagonist and non-genotoxic carcinogen
  26. GC48801 Nylidrin

    脑清

    An agonist of β-ARs and antagonist of NR1A/2B subunit-containing NMDA receptors
  27. GC48790 Ticlopidine-d4 (hydrochloride)

    盐酸噻氯匹定 d4 (盐酸盐)

    An internal standard for the quantification of ticlopidine
  28. GC48774 Melicopine An acridone alkaloid with antimalarial and anticancer activities
  29. GC48771 Avobenzone-13C-d3

    BMDBM-13C-d3, Butyl Methoxydibenzoylmethane-13C-d3

    An internal standard for the quantification of avobenzone
  30. GC48769 7,10-dihydroxy-8(E)-Octadecenoic Acid An antibacterial hydroxy fatty acid
  31. GC48764 Sydowinin B

    MS-347b

    A xanthone polyketide with immunosuppressant activity
  32. GC48752 Isothipendyl (hydrochloride)

    盐酸异西喷他

    An antihistamine
  33. GC48744 Gliclazide-d4

    格列齐特 d4

    An internal standard for the quantification of gliclazide
  34. GC48742 Penipurdin A An anthraquinone with antibacterial activity
  35. GC48719 (S)-Canadine

    四氢小檗碱,(-)-Canadine; (S)-(-)-Canadine

    An alkaloid with insecticidal activity
  36. GC48715 ITH15004 A P2X7 receptor antagonist
  37. GC48711 Trypacidin A fungal metabolite
  38. GC48703 Palmarumycin C3 A fungal metabolite
  39. GC48693 Rubiginone D2 A polyketide with antibacterial and anticancer activities
  40. GC48689 SBP-7455 A dual inhibitor of ULK1 and ULK2
  41. GC48688 Griseofulvin-d3

    灰黄霉素 d3

    An internal standard for the quantification of griseofulvin
  42. GC48684 Pipemidic Acid (hydrate)

    吡哌酸三水合物

    An antibiotic
  43. GC48677 Sulindac-d3

    MK-231-d3

    An internal standard for the quantification of sulindac
  44. GC48676 Monascuspiloin

    Monascinol

    A fungal metabolite with anticancer activity
  45. GC48667 Nanangenine C A drimane sesquiterpene
  46. GC48664 Enoxacin-d8 (hydrochloride) An internal standard for the quantification of enoxacin
  47. GC48660 Nanangenine F A drimane sesquiterpene
  48. GC48659 Umbelliprenin

    7-Farnesyloxycoumarin

    A prenylated coumarin with diverse biological activities
  49. GC48652 Olomoucine II

    2-[[[2-[[(1R)-1-(羟基甲基)丙基]氨基]-9-(1-甲基乙基)-9H-嘌呤-6-基]氨基]甲基]苯酚

    A CDK inhibitor
  50. GC48650 DTUN A lipophilic hyponitrite radical initiator
  51. GC48642 Tedizolid-13C-d3

    TR 700-13C,d3; Torezolid-13C,d3; DA-7157-13C,d3

    An internal standard for the quantification of tedizolid

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