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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. GC48639 Lornoxicam-d4

    氯诺昔康-D4,Chlortenoxicam-d4; Ro 13-9297-d4

    An internal standard for the quantification of lornoxicam
  3. GC48619 Nanangenine B A drimane sesquiterpene
  4. GC48618 Isonanangenine B

    SF002-96-1

    A drimane sesquiterpene lactone
  5. GC48614 IMP-1710 A clickable UCH-L1 inhibitor
  6. GC48611 Ambroxol-d5

    盐酸氨溴索D5

    An internal standard for the quantification of ambroxol
  7. GC48610 GSK3987 A dual agonist of LXRα and LXRβ
  8. GC48593 Cefprozil-d4 An internal standard for the quantification of cefprozil
  9. GC48580 Penicolinate B

    Penicolinate A monomethyl ester

    A fungal metabolite with diverse biological activities
  10. GC48565 Ofloxacin-d8 (hydrochloride)

    Hoe-280-d8 hydrochloride

    An internal standard for the quantification of ofloxacin
  11. GC48554 Isoreserpiline

    3-Isoreserpilinic Acid, methyl ester, Neoreserpiline

    An indole alkaloid with diverse biological activities
  12. GC48547 Sartorypyrone D A fungal metabolite
  13. GC48546 Emeguisin A A fungal metabolite
  14. GC48528 Piericidin B A bacterial metabolite with insecticidal and antimicrobial activities
  15. GC48523 HSGN-218 A gut-restrictive antibiotic
  16. GC48520 Betulonaldehyde

    白桦脂醛,半合成

    A pentacyclic triterpenoid
  17. GC48516 Nafcillin-d5 (sodium salt) An internal standard for the quantification of nafcillin
  18. GC48511 Avrainvillamide

    (+)-Avrainvillamide; CJ-17,665

    A fungal metabolite
  19. GC48509 Apigenin 7-O-Glucuronide (hydrate) Apigenin 7-O-glucuronide is a flavonoid that has been found in J
  20. GC48507 Kaempferol 3-O-galactoside

    三叶豆苷,Trifolin

    A flavonoid with diverse biological activities
  21. GC48504 Betulinic Aldehyde oxime

    桦木醛肟,半合成

    A derivative of betulin
  22. GC48503 28-Deoxybetulin methyleneamine A derivative of betulin
  23. GC48501 Preterramide C A fungal metabolite
  24. GC48498 Sarpogrelate-d3 (hydrochloride)

    MCI-9042-d3

    An internal standard for the quantification of sarpogrelate
  25. GC48496 Clobetasol Propionate-d5

    CCI-4725-d5, CGP 9555-d5, Clobetasol 17-propionate-d5

    An internal standard for the quantification of clobetasol propionate
  26. GC48495 BMS-P5 A PAD4 inhibitor
  27. GC48493 PCI 45227

    依鲁替尼代谢物,PCI-45227

    An active metabolite of ibrutinib
  28. GC48489 Cefadroxil-d4 (trifluoroacetate salt) An internal standard for the quantification of cefadroxil
  29. GC48488 3-Oxobetulin Acetate

    28-O-acetyl-3-Oxobetulin, 3-oxo-28-O-Acetylbetulin

    A derivative of betulin
  30. GC48484 Neosartoricin A prenylated tricyclic polyketide
  31. GC48482 28-Acetylbetulin

    28-acetoxy Betulin, 28-O-Acetylbetulin, C-28-Acetylbetulin

    A lupane triterpenoid with anti-inflammatory and anticancer activities
  32. GC48472 Aranciamycin A An antibiotic
  33. GC48470 Ac-DEVD-CHO (trifluoroacetate salt)

    N-Ac-Asp-Glu-Val-Asp-CHO

    A dual caspase-3/caspase-7 inhibitor
  34. GC48464 GC376 (sodium salt) An inhibitor of 3C- and 3C-like proteases
  35. GC48461 rac-trans-4-hydroxy Glyburide

    4-trans-hydroxycyclohexyl Glyburide, 4-trans-hydroxy Glibenclamide

    An active metabolite of glyburide
  36. GC48458 Betulinic glycine amide A derivative of betulinic acid
  37. GC48457 3-keto Fusidic Acid

    3-酮基夫西地酸(欧洲药典标准品)

    An active metabolite of fusidic acid
  38. GC48452 Taurocholic Acid-d4 MaxSpec® Standard

    N-Choloyltaurine-d4

    A quantitative analytical standard guaranteed to meet MaxSpec identity, purity, stability, and concentration specifications
  39. GC48449 28-(Poc-amino)betulin An alkyne derivative of betulin
  40. GC48447 TAS 205 An inhibitor of H-PGDS
  41. GC48445 Hygromycin B (hydrate) An aminoglycoside antibiotic
  42. GC48443 Cefsulodin (sodium salt hydrate)

    头孢磺吡苄钠盐

    A cephalosporin antibiotic
  43. GC48442 Tryptoquivaline D

    Nortryptoquivaline, NSC 292204

    A fungal metabolite with anticancer activity
  44. GC48439 IMP-1700 An inhibitor of bacterial DNA repair
  45. GC48437 4'-Acetyl Chrysomycin A A bacterial metabolite with antibacterial and anticancer activities
  46. GC48436 4'-Acetylchrysomycin B A bacterial metabolite with antibacterial and anticancer activities
  47. GC48435 5-Bromo-4-chloro-3-indolyl-β-D-Glucuronide (cyclohexylammonium salt hydrate)

    BCIG, X-GLUC

    A chromogenic substrate for β-glucuronidase
  48. GC48434 Elsinochrome A

    痂囊腔菌素AELSINOCHROMEA

    A fungal metabolite
  49. GC48433 BX-320

    N1-[3-[[5-溴-2-[[3-[(1-吡咯烷基羰基)氨基]苯基]氨基]-4-嘧啶基]氨基]丙基]-2,2-二甲基丙烷二酰胺

    An inhibitor of PDK1
  50. GC48431 Talaromycesone A A fungal metabolite
  51. GC48430 Ac-DEVD-CMK (trifluoroacetate salt)

    AcAspGluValAspCMK, Caspase3 Inhibitor III

    An inhibitor of caspase-3

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