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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. GC49372 Kaempferol 7-neohesperidoside

    山柰酚-7-O-新橙皮糖苷

    A flavonoid glycoside with antioxidant and anticancer activities
  3. GC49368 L-Methionine-d3

    L-蛋氨酸-d3

    An internal standard for the quantification of L-methionine
  4. GC49365 25-Desacetyl Rifampicin

    25-乙酰-3-[(五)-[(4-甲基-1-哌嗪基)亚胺]甲基]利福霉素

    A major active metabolite of rifampicin
  5. GC49364 3-Hydroxycoumarin

    3-羟基香豆素

    A coumarin with diverse biological activities
  6. GC49360 Antimycin A Complex

    抗霉素

    一种细菌代谢物复合物

  7. GC49344 Fisetin-d5 An internal standard for the quantification of fisetin
  8. GC49343 Isoproterenol-d7 (hydrochloride)

    Isoprenaline-d7

    An internal standard for the quantification of isoproterenol
  9. GC49341 Spermidine-d6 An internal standard for the quantification of spermidine
  10. GC49339 5(6)-Carboxy-2′,7′-dichlorofluorescein diacetate

    5[6]-羧基-2',7'-二氯荧光素二乙酸酯

    An oxidant-sensitive fluorescent probe
  11. GC49337 4-Acetamidobenzenesulfonamide

    对乙酰胺基苯磺酰胺

    A metabolite of asulam and sulfanilamide
  12. GC49336 AMK (hydrochloride)

    N-γ-acetyl-5-Methoxykynurenamine, N1-acetyl-5-Methoxykynuramine

    An active metabolite of melatonin
  13. GC49333 SH-42 An inhibitor of DHCR24
  14. GC49329 Turkesterone (hydrate) A phytoecdysteroid with diverse biological activities
  15. GC49314 Arecaidine propargyl ester (hydrobromide)

    1,2,5,6-四氢-1-甲基-3-吡啶羧酸2-丙炔-1-基酯氢溴酸盐

    A muscarinic M2 agonist
  16. GC49313 Picosulfate (sodium salt hydrate)

    匹可硫酸钠一水合物

    A stimulant laxative and prodrug form of desacetyl bisacodyl
  17. GC49312 7-Fluoro-2,1,3-benzoxadiazole-4-sulfonate (ammonium salt)

    7-苯并呋咱-4-磺酸铵

    A thiol-reactive fluorogenic probe
  18. GC49309 A-943931 (hydrochloride hydrate) A histamine H4 receptor antagonist
  19. GC49308 Ungeremine

    石蒜碱内铵盐

    A betaine-type alkaloid with diverse biological activities
  20. GC49306 Isopimaric Acid

    异海松酸

    A diterpenoid resin acid
  21. GC49303 Ganoderic Acid DM

    灵芝酸 DM

    A triterpenoid with diverse biological activities
  22. GC49302 Bactenecin (bovine) (trifluoroacetate salt)

    H-Arg-Leu-Cys-Arg-Ile-Val-Val-Ile-Arg-Val-Cys-Arg-OH, RLCRIVVIRVCR-OH

    A cationic peptide
  23. GC49294 1-(4-Chlorobenzhydryl)piperazine

    1-(4-氯二苯甲基)哌嗪

    An inactive metabolite of meclizine and chlorcyclizine
  24. GC49290 Indoxyl Sulfate-d5 (potassium salt) An internal standard for the quantification of indoxyl sulfate
  25. GC49289 Dolutegravir O-β-D-Glucuronide

    Dolutegravir Glucuronide, DTG Glucuronide

    A metabolite of dolutegravir
  26. GC49288 Dolutegravir M1

    多替拉韦杂质

    A metabolite of dolutegravir
  27. GC49287 Faropenem (sodium salt hydrate)

    法罗培南钠2.5水合物

    A penem antibiotic
  28. GC49285 Adenosine 5’-methylenediphosphate (hydrate)

    Adenosine 5'-(α,β-methylene)diphosphate, AMP-CP, APCP, 5'-APCP

    An inhibitor of ecto-5’-nucleotidase
  29. GC49284 GSK-A1 A PI4KIIIα inhibitor
  30. GC49283 2-O-(α-D-Glucopyranosyl)glycerol

    Glucosylglycerol, Glycoin

    A compatible solute
  31. GC49282 Hydroxy Lenalidomide

    羟基来那度胺

    A metabolite of lenalidomide
  32. GC49279 Resolvin D2 n-3 DPA

    7(S),16(R),17(S)-Resolvin D2 n-3 DPA, RvD2 n-3 DPA

    A specialized pro-resolving mediator
  33. GC49275 8-Oxycoptisine

    8-氧黄连碱

    An isoquinoline alkaloid with anticancer and gastroprotective activities
  34. GC49274 Cefalonium

    头孢洛宁

    A cephalosporin antibiotic
  35. GC49271 Glufosinate-d3 (hydrochloride) An internal standard for the quantification of glufosinate
  36. GC49270 Nicotinamide-d4

    氘代烟酰胺,Niacinamide-d4; Nicotinic acid amide-d4

    An internal standard for the quantification of nicotinamide
  37. GC49268 (+)-δ-Cadinene

    Δ-杜松烯

    A sesquiterpene with antimicrobial and anticancer activities
  38. GC49267 Hygromycin B-d4 An internal standard for the quantification of hygromycin
  39. GC49266 Compstatin (trifluoroacetate salt)

    ICVVQDWGHHRCT

    A peptide inhibitor of complement activation
  40. GC49265 PKI (14-22) amide (myristoylated) (trifluoroacetate salt)

    Myr-Gly-Arg-Thr-Gly-Arg-Arg-Asn-Ala-Ile-NH2, Myr-GRTGRRNAI-NH2, Myristoylated PKI-(14-22)-amide, PKI-(Myr-14-22)-amide

    A PKA inhibitor
  41. GC49263 Ac2-26 (human) (ammonium salt)

    Ac-AMVSEFLKQAWFIENEEQEYVQTVK-OH, Ac-ANX-A12-26, N-Acetyl-AMVSEFLKQAWFIENEEQEYVQTVK

    An annexin A1-mimetic peptide
  42. GC49259 Antagonist G (trifluoroacetate salt)

    Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH2, Arg6,D-Trp7,9,NmePhe8-substance P (6-11)

    A neuropeptide antagonist
  43. GC49256 N-acetyl Lenalidomide

    N-乙酰来那度胺

    A metabolite of lenalidomide
  44. GC49251 Oxaliplatin-d10

    Lipoxal-d10

    An internal standard for the quantification of oxaliplatin
  45. GC49244 4-oxo Isotretinoin

    4-酮13-顺式维甲酸

    An active metabolite of isotretinoin
  46. GC49243 Quassin

    苦木素,Nigakilactone D

    A quassinoid with diverse biological activities
  47. GC49241 Methyl Diethyldithiocarbamate

    S-甲基N,N二乙基二硫代氨基甲酸

    An active metabolite of disulfiram
  48. GC49238 93-O17S An ionizable cationic lipidoid
  49. GC49237 93-O17O An ionizable cationic lipidoid
  50. GC49235 6-Methylmercaptopurine

    6-甲巯基嘌呤

    A metabolite of 6-mercaptopurine
  51. GC49233 5-Feruloylquinic Acid

    5-O-阿魏酰奎尼酸

    A chlorogenic acid with antioxidant activity

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