Immunology/Inflammation
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
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GC70170
Zilucoplan
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GC70154
Yakuchinone A
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GC70120
Vixarelimab
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GC70119
Vipoglanstat
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GC70116
Vesencumab
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GC70045
Tozorakimab
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GC70026
Thymidine 3',5'-diphosphate tetrasodium
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GC70017
Tesidolumab
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GC70004
Tebentafusp
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GC69998
TBK1-IN-1
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GC69963
STING agonist-8 dihydrochloride
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GC69962
STING agonist-3 trihydrochloride
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GC69961
STING agonist-22
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GC69959
STING agonist-20
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GC69943
SRI-42127
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GC69937
Spesolimab
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GC69912
SLC7A11-IN-1
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GC69908
Skatole-d3
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GC69899
SIRT6 activator 12q
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GC69889
Sifalimumab
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GC69841
Rubropunctatin
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GC69831
ROS-ERS inducer 1
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GC69828
Rolinsatamab
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GC69823
(R)-(-)-Ibuprofen-d3
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GC69818
Risankizumab
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GC69803
Ravulizumab
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GC69799
(Rac)-ZLc-002
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GC69713
Pivekimab
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GC69705
Physalin A
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GC69684
Pelecopan
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GC69641
Oxelumab
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GC69631
Ordesekimab
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GC69621
Olokizumab
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GC69615
ODN D-SL03
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GC69613
ODN 6016
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GC69595
NSC61610
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GC69592
NRP1 antagonist 1
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GC69590
Nrf2 activator-2
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GC69582
ARC186
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GC69573
NLRP3-IN-18
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GC69572
NLRP3-IN-13
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GC69571
NLRP3-IN-11
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GC69570
NLRP3-IN-10
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GC69569
NLRP3/AIM2-IN-2
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GC69561
Nidanilimab
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GC69556
NF-κB/MAPK-IN-1
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GC69555
NF-κB-IN-4
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GC69539
Nasunin
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GC69534
Nadunolimab
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GC69530
N-Acetyldopamine dimer-2
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GN10814
Quercitrin
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GN10805
Protopanaxdiol
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GN10804
Isovitexin
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GN10799
Ginsenoside Rg3
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GN10784
Rhoifolin
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GN10778
Picroside II
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GN10759
Sanggenone C
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GN10741
Garcinone D
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GN10737
Tanshinone IIA
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GN10727
Forsythoside B
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GN10718
Andrographolide
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GN10706
Diosimin
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GN10698
Cynarin
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GN10693
Rutin
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GN10685
Anemarsaponin B
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GN10669
Glucosamine sulfate
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GN10668
Coenzyme Q10
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GN10664
Honokiol
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GN10662
Cichoric Acid
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GN10650
Ziyuglycoside II
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GN10646
Engeletin
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GN10627
Atractylenolide I
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GN10614
Ginsenoside Rg2
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GN10613
Hesperidin
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GN10599
Procyanidin B2
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GN10584
Ginsenoside Rk1
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GN10582
Liquiritin
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GN10579
Aristolochic Acid A
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GN10569
Lobetyolin
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GN10550
Neosperidin dihydrochalcone
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GN10549
Ginsenoside Rd
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GN10544
Ginsenoside Rg1
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GN10538
Ginsenoside Rh1
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GN10536
Aconine
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GN10534
Asiaticoside
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GN10523
Berberine Sulfate
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GN10519
Ethyl ferulate
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GN10518
Chitosamine hydrochloride
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GN10509
Apigenin-7-O-β-D-glucopyranoside
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GN10504
Echinocystic acid
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GN10503
Piceatannol
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GN10491
Mangiferin
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GN10484
Amentoflavone
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GN10475
Rhein
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GN10450
Ginsenoside F3
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GN10448
Lycopene
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GN10443
Berbamine
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GN10442
Curculigoside
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GN10436
Morusin
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GN10429
Neochlorogenic acid