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
- 5-Lipoxygenase(10)
- Papain(1)
- PGDS(1)
- PGE synthase(24)
- SIKs(11)
- IκB/IKK(64)
- AP-1(6)
- KEAP1-Nrf2(65)
- NOD1(1)
- TLR(139)
- NF-κB(235)
- Interleukin Related(167)
- 15-lipoxygenase(2)
- Others(63)
- Aryl Hydrocarbon Receptor(35)
- CD73(14)
- Complement System(57)
- Galectin(12)
- IFNAR(25)
- NO Synthase(74)
- NOD-like Receptor (NLR)(50)
- STING(104)
- Reactive Oxygen Species(454)
- Apoptosis(780)
- FKBP(20)
- eNOS(5)
- iNOS(29)
- nNOS(20)
- Glutathione(55)
- Adaptive Immunity(209)
- Allergy(124)
- Arthritis(34)
- Autoimmunity(179)
- Gastric Disease(95)
- Immunosuppressants(37)
- Immunotherapeutics(4)
- Innate Immunity(560)
- Pulmonary Diseases(108)
- Reactive Nitrogen Species(50)
- Reactive Sulfur Species(28)
- Specialized Pro-Resolving Mediators(50)
- Cyclic GMP-AMP Synthase(2)
- BCL6(3)
- CD20(3)
- CD28(1)
- FAP(7)
- PSMA(7)
- Nuclear Factor of activated T Cells (NFAT)(1)
- Glycoprotein VI(1)
- Tim3(2)
- Hapten(1)
- Nectin-4(2)
- Cat.No. 产品名称 Information
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GC48911
Tubermycin B
吩嗪-1-羧酸
A bacterial metabolite with antifungal and fungicidal activities -
GC48910
2-Hydroxyanthraquinone
2-羟基蒽醌
An anthraquinone with antibacterial and estrogenic activities -
GC48908
Ornidazole-d5
Ro 7-0207-d5
An internal standard for the quantification of ornidazole -
GC48907
Metaxalone-d6
AHR438-d6; NSC170959-d6
An internal standard for the quantification of metaxalone -
GC48900
Isocurcumenol
异莪术烯醇
A sesquiterpene with diverse biological activities -
GC48896
Nitrofurantoin-13C3
硝基呋喃妥因-13C3
An internal standard for the quantification of nitrofurantoin -
GC48894
SIH
2-异丙基噻吨酮
An iron chelator -
GC48893
Carbazomycin B
A bacterial metabolite with diverse biological activities
-
GC48889
Methazolamide-d6
L584601-d6
An internal standard for the quantification of methazolamide -
GC48880
7-Methoxyflavone
7-甲氧基黄酮
A flavone with diverse biological activities -
GC48878
Carbazomycin A
A bacterial metabolite with diverse biological activities
-
GC48857
Methylchloroisothiazolinone/Methylisothiazolinone Mixture
CMIT/MIT, MCI/MI, MCIT/MIT
A mixture of isothiazolinone biocides -
GC48856
Fenspiride-d5
Decaspiride-d5
An internal standard for the quantification of fenspiride -
GC48853
Pirlindole-d4 (hydrochloride)
An internal standard for the quantification of pirlindole
-
GC48850
Carbazomycin C
A bacterial metabolite with diverse biological activities
-
GC48848
Albendazole-d7
阿苯达唑-D7,SKF-62979-d7
An internal standard for the quantification of albendazole -
GC48842
Actiphenol
放线菌酚
A bacterial metabolite with antiviral activity -
GC48841
Arbutin-d4
β-Arbutin-d4
An internal standard for the quantification of arbutin -
GC48839
Nifuroxazide-d4
硝呋齐特 d4
An internal standard for the quantification of nifuroxazide -
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 -
GC48827
Flufenamic Acid-d4
FFA-d4, Fluphenamic Acid-d4
An internal standard for the quantification of flufenamic acid -
GC48826
Carbazomycin D
A bacterial metabolite with diverse biological activities
-
GC48815
5,7,8-Trimethoxydictamnine
Acronycidine, NSC 30619
A quinoline alkaloid with antimalarial activity -
GC48805
Methapyrilene (hydrochloride)
盐酸美沙吡林,Thenylpyramine hydrochloride
An H1 receptor antagonist and non-genotoxic carcinogen -
GC48801
Nylidrin
脑清
An agonist of β-ARs and antagonist of NR1A/2B subunit-containing NMDA receptors -
GC48790
Ticlopidine-d4 (hydrochloride)
盐酸噻氯匹定 d4 (盐酸盐)
An internal standard for the quantification of ticlopidine -
GC48774
Melicopine
An acridone alkaloid with antimalarial and anticancer activities
-
GC48771
Avobenzone-13C-d3
BMDBM-13C-d3, Butyl Methoxydibenzoylmethane-13C-d3
An internal standard for the quantification of avobenzone -
GC48769
7,10-dihydroxy-8(E)-Octadecenoic Acid
An antibacterial hydroxy fatty acid
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GC48764
Sydowinin B
MS-347b
A xanthone polyketide with immunosuppressant activity -
GC48752
Isothipendyl (hydrochloride)
盐酸异西喷他
An antihistamine -
GC48744
Gliclazide-d4
格列齐特 d4
An internal standard for the quantification of gliclazide -
GC48742
Penipurdin A
An anthraquinone with antibacterial activity
-
GC48719
(S)-Canadine
四氢小檗碱,(-)-Canadine; (S)-(-)-Canadine
An alkaloid with insecticidal activity -
GC48715
ITH15004
A P2X7 receptor antagonist
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GC48711
Trypacidin
A fungal metabolite
-
GC48703
Palmarumycin C3
A fungal metabolite
-
GC48693
Rubiginone D2
A polyketide with antibacterial and anticancer activities
-
GC48689
SBP-7455
A dual inhibitor of ULK1 and ULK2
-
GC48688
Griseofulvin-d3
灰黄霉素 d3
An internal standard for the quantification of griseofulvin -
GC48684
Pipemidic Acid (hydrate)
吡哌酸三水合物
An antibiotic -
GC48677
Sulindac-d3
MK-231-d3
An internal standard for the quantification of sulindac -
GC48676
Monascuspiloin
Monascinol
A fungal metabolite with anticancer activity -
GC48667
Nanangenine C
A drimane sesquiterpene
-
GC48664
Enoxacin-d8 (hydrochloride)
An internal standard for the quantification of enoxacin
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GC48660
Nanangenine F
A drimane sesquiterpene
-
GC48659
Umbelliprenin
7-Farnesyloxycoumarin
A prenylated coumarin with diverse biological activities -
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 -
GC48650
DTUN
A lipophilic hyponitrite radical initiator
-
GC48642
Tedizolid-13C-d3
TR 700-13C,d3; Torezolid-13C,d3; DA-7157-13C,d3
An internal standard for the quantification of tedizolid