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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. GP26368 Tri a 14.0101 Recombinant Non-Specific Lipid-Transfer Protein Tri a 14 produced in SF9 is a glycosylated, polypeptide chain having a calculated molecular mass of 13kDa
  3. GP26367 Pen a 1.0101 Recombinant Tropomyosin Pen a 1
  4. GP26366 MALD3 Recombinant Non-Specific Lipid-Transfer Protein Mal d 3 produced in SF9 is a glycosylated, polypeptide chain having a calculated molecular mass of 12kDa
  5. GP26365 Cor a 14.0101 Recombinant 2S albumin produced in SF9 is a glycosylated, polypeptide chain having a calculated molecular mass of 14kDa
  6. GP26364 Cor a 9 The native protein Corylus Avellana Cor a 9 is purified from hazelnut by protein chemical methods
  7. GP26363 Cor a 8.0101 Recombinant Non-specific Lipid-Transfer Protein Cor a 8 produced in SF9 is a glycosylated, polypeptide chain having a calculated molecular mass of 11kDa
  8. GP26025 LGALS3 Mouse, Active LGALS3 Mouse Recombinant produced in E
  9. GP26024 LGALS2 Mouse, Active LGALS2 Mouse Recombinant produced in E
  10. GC26091 ZLc002 ZLc-002 is a selective inhibitor of nNOS-Capon coupling. ZLc-002 suppresses inflammatory nociception and chemotherapy-induced neuropathic pain.
  11. GC25314 CU-CPD107 CU-CPD107 is a selective, dual-activity small-molecule which demonstrated differential activity against the TLR8 agonists and ssRNA ligands. In the presence of R848, CU-CPD107 acts as a TLR8 signaling inhibitor (IC50=13.7 μM). In the presence of ssRNA, CU-CPD107 shows synergistic agonist activities, while CU-CPD107 alone is unable to influence TLR8 signaling.
  12. GC25014 3',3'-cGAMP 3',3'-cGAMP (3',3'-cyclic GMP-AMP, Cyclic GMP-AMP, cGAMP) activates the endoplasmic reticulum (ER)-resident receptor stimulator of interferon genes (STING), thereby inducing an antiviral state and the secretion of type I IFNs.
  13. GC67968 ALPK1-IN-2
  14. GC67966 Methylstat
  15. GC67936 Lupiwighteone
  16. GC67903 RIDR-PI-103
  17. GC67892 CHD-5
  18. GC67890 PHA 408
  19. GC67859 Clerodendrin
  20. GC67792 NSC49652
  21. GC67748 Brodalumab
  22. GC67721 CP-447697
  23. GC67719 SN-001
  24. GC67699 TLR8 agonist 5
  25. GC52516 Erbstatin A tyrosine kinase inhibitor
  26. GC52514 Arachidonic Acid-d11 ethyl ester An internal standard for the quantification of arachidonic acid ethyl ester
  27. GC52505 Ganglioside GT1b (bovine) (sodium salt) A sphingolipid
  28. GC52501 2',3'-Dideoxyadenosine 5'-triphosphate (lithium salt) An inhibitor of reverse transcriptases and DNA polymerases
  29. GC52499 Abz-Ala-Pro-Glu-Glu-Ile-Met-Arg-Arg-Gln-EDDnp (trifluoroacetate salt) A sensitive substrate for neutrophil elastase
  30. GC52496 Sulfatide (bovine) (sodium salt) A mixture of isolated bovine sulfatides
  31. GC52492 Globotriaosylceramide (hydroxy) (porcine RBC) A sphingolipid
  32. GC52491 Globotriaosylceramide (non-hydroxy) (porcine RBC) A sphingolipid
  33. GC52489 Ceramide (hydroxy) (bovine spinal cord) A sphingolipid
  34. GC52487 Ganglioside GM4 (chicken egg) (ammonium salt) A sphingolipid
  35. GC52486 Ceramide Phosphoethanolamine (bovine) A sphingolipid
  36. GC52485 Ceramide (non-hydroxy) (bovine spinal cord) A sphingolipid
  37. GC52483 Fucosylated Ganglioside GM1 (porcine) (ammonium salt) A sphingolipid
  38. GC52476 Bax Inhibitor Peptide V5 (trifluoroacetate salt) A Bax inhibitor
  39. GC52475 Zanamivir-13C,15N2 (hydrate) An internal standard for the quantification of zanamivir
  40. GC52473 NVP-AAM077 An NMDA receptor antagonist
  41. GC52472 Inostamycin A (sodium salt) A bacterial metabolite with anticancer activity
  42. GC52471 7(S),10(S)-DiHOME An antibacterial hydroxy fatty acid
  43. GC52469 CL2A-SN-38 (dichloroacetic acid salt) An antibody-drug conjugate containing SN-38
  44. GC52468 Benanomicin B A microbial metabolite with antifungal, fungicidal, and antiviral activities
  45. GC52467 Cell Death Screening Library For screening a variety of cell death pathways
  46. GC52457 WRW4 (trifluoroacetate salt) A peptide antagonist of FPR2 and FPR3
  47. GC52455 Pixantrone-d8 (maleate) An internal standard for the quantification of pixantrone
  48. GC52446 2-Nonylquinolin-4(1H)-one-d4 An internal standard for the quantification of 2-nonylquinolin-4(1H)-one
  49. GC52445 2-nonyl-3-hydroxy-4-Quinolone-d4 An internal standard for the quantification of 2-nonyl-3-hydroxy-4-quinolone
  50. GC52442 (D)-PPA 1 (trifluoroacetate salt) An inhibitor of the PD-1-PD-L1 protein-protein interaction
  51. GC52436 TRAP-6 amide (trifluoroacetate salt) A peptide PAR1 agonist

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