Immune response - TLR3 and TLR4 induce TICAM1-specific signaling pathway

Click on a target from the pathway image to view related information. Zoom     View Legend

photo_map
 


Human PrimePCR Selections
photo_fpc
TLR3 and TLR4 induce TICAM1 Signaling Pathway H96

Predesigned 96-well panel for use with SYBR® Green

 

List Price:  $366.00

 

Your Price : Log In

photo_fpc
TLR3 and TLR4 induce TICAM1 Signaling Pathway H384

Predesigned 384-well panel for use with SYBR® Green

 

List Price:  $496.00

 

Your Price : Log In

Role of TLRs 3 and 4 in cell antiviral response: TICAM1-specific signaling pathways

Toll-like receptors (TLR) initiate signaling cascades through recognition of a variety of microbial components, thus serving as an important link between innate and adaptive immune responses. Each TLR recognizes distinct ligands by means of its leucine-rich repeats and elicits different, but often overlapping immune responses [1].

TLR3-induced signaling pathways are triggered by binding of virus-derived double-stranded RNA [1], whereas TLR4 becomes activated after binding to number of bacterial cell wall components: Lipopolysaccharide (LPS) [1], Pulmonary surfactant-associated protein A (PSAP) [2], Paclitaxel [3], Fibronectin [4], Pneumolysin [5].

Although Myeloid differentiation primary response gene 88 (MyD88)-dependent signaling pathway is common for all TLRs, TLR3- and TLR4-induced activation of the transcription factor nuclear factor kappa B (NF-kB) can be mediated by some alternative adaptors. It can be activated by TLR3 ligands via Toll-like receptor adaptor molecule 1 (TRIF (TICAM1)) [1]. TLR4 signaling can also be mediated by TRIF (TICAM1), which binds to TLR4 adaptor Toll-like receptor adaptor molecule 2 (TRAM) [6]. In addition TLRs are able to induce autophagy through TRIF (TICAM1) - Beclin 1 interaction [7]. TLR4 activates NF-kB independently of TRIF (TICAM1) through its other adaptor, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP (Mal)) [8]. TRIF (TICAM1)-dependent NF-kB activation is mediated either by TNF receptor-associated factor 6 (TRAF6) or by Receptor TNFRSF-interacting serine-threonine kinase 1 (RIPK1)-induced kinase cascade [1]. Moreover, TRIF (TICAM1) causes activation of transcription factor Interferon regulatory factor 3 (IRF3) [9]. Both IRF3 and NF-kB regulate expression of such proinflammatory molecules as Interferon alpha and beta (IFN-alpha and IFN-beta), thus mediating the antiviral action of interferon.

References:

  1. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, Tschopp J
    RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nature immunology 2004 May;5(5):503-7
  2. Guillot L, Balloy V, McCormack FX, Golenbock DT, Chignard M, Si-Tahar M
    Cutting edge: the immunostimulatory activity of the lung surfactant protein-A involves Toll-like receptor 4. Journal of immunology (Baltimore, Md. : 1950) 2002 Jun 15;168(12):5989-92
  3. Takeuchi O, Akira S
    Toll-like receptors; their physiological role and signal transduction system. International immunopharmacology 2001 Apr;1(4):625-35
  4. Lee J, Chuang TH, Redecke V, She L, Pitha PM, Carson DA, Raz E, Cottam HB
    Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Proceedings of the National Academy of Sciences of the United States of America 2003 May 27;100(11):6646-51
  5. Malley R, Henneke P, Morse SC, Cieslewicz MJ, Lipsitch M, Thompson CM, Kurt-Jones E, Paton JC, Wessels MR, Golenbock DT
    Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Proceedings of the National Academy of Sciences of the United States of America 2003 Feb 18;100(4):1966-71
  6. Oshiumi H, Sasai M, Shida K, Fujita T, Matsumoto M, Seya T
    TIR-containing adapter molecule (TICAM)-2, a bridging adapter recruiting to toll-like receptor 4 TICAM-1 that induces interferon-beta. The Journal of biological chemistry 2003 Dec 12;278(50):49751-62
  7. Shi CS, Kehrl JH
    MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. The Journal of biological chemistry 2008 Nov 28;283(48):33175-82
  8. Jefferies CA, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, Walch E, Wirth T, O'Neill LA
    Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4. The Journal of biological chemistry 2003 Jul 11;278(28):26258-64
  9. Jiang Z, Mak TW, Sen G, Li X
    Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta. Proceedings of the National Academy of Sciences of the United States of America 2004 Mar 9;101(10):3533-8

Target Details

Click on a target from the pathway image to view related information.

[ Close ]
Click here to print
[ Close ]
Click here to print
 

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined

undefined

undefined

My PrimePCR Hot List stores your saved PrimePCR products and configurations

undefined