Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFκB and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR

Jiang, Zhengfan; Zamanian-Daryoush, Maryam; Nie, Huiqing; Silva, Aristóbolo M.; Williams, Bryan R.G.; Li, Xiaoxia

doi:10.1016/s0021-9258(20)86377-7

Cited by 6 publications

(6 citation statements)

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“…We found that PKR is 2.5-fold more abundant in MZ B cells compared to the other analysed subsets. Interestingly, PKR integrates sensing of double-stranded RNAs to NF□B and MAP kinase activation 61,78 , as well as controlling translation via phosphorylation of eIF2α. Considering that MZ B cells also uniquely express TLR3, further investigation of how PKR impacts the activation of MZ B cells is warranted.…”

Section: Discussionmentioning

confidence: 99%

An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells

Salerno

Howden

Matheson

et al. 2022

Preprint

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During B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune responses. We used label-free mass spectrometry to quantify the proteome of B cell subsets from the mouse spleen and map the differential expression of environmental sensing, transcription- and translation initiation-factors that define cellular identity and function. By comparing the full-length transcriptome and proteome within the same sample, we identified mRNAs linked to B cell activation and antibody secretion that are expressed without detectable protein. These "poised" mRNAs might enable rapid protein production through increased translation or protein stability. In addition, through interrogation of our proteomic dataset, we found that the translational repressor PDCD4 restrains the response of marginal zone B cells to a T-independent antigen. Our molecular characterization of B cell maturation is a valuable resource to further explore the mechanisms underpinning the specialised functions of B cell subsets.

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Section: Discussionmentioning

confidence: 99%

An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells

Salerno

Howden

Matheson

et al. 2022

Preprint

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“…Trif-induced NF-kB activation may proceed through two ways. First, Trif recruits tumor necrosis factor receptor (TNF-R) associated factor (TRAF)-6 by means of its N-terminal region (Jiang et al, 2003;Sato et al, 2003). However, the significance of TRAF6 in this context is still unclear due to the potential redundancy provided by other TRAF molecules (Gohda et al, 2004;Hacker et al, 2006).…”

Section: Detection Of Dsrna and Signaling Through Tlr3mentioning

confidence: 99%

Toll-Like Receptors and RNA Helicases: Two Parallel Ways to Trigger Antiviral Responses

2006

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The early detection by the host of invading microorganisms, including viruses, depends on a limited number of specific receptors that recognize pathogen-associated molecular patterns (PAMPs). A few of these PAMPs, including ssRNA and dsRNA, are recognized by Toll-like receptors (TLR)-7/8 and TLR3, respectively. Activation of an antiviral TLR-dependent signaling cascade leads to the activation of the key transcription factors IRF and NF-kappaB, which promote antiviral responses through induction of specific genes. Recently, a second system has been described, which relies on the cytoplasmic recognition of dsRNA by RNA helicases such as RIG-I. In this review, we discuss the mechanistic aspects of these important arms of the host innate response to dsRNA and a few viral strategies utilized to counteract them.

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“…When phosphorylated by IRAK-4, IRAK-1 interacts with TRAF6 (TNF receptorassociated factor 6; Cao et al, 1996;Li et al, 2002) and disengages from the receptor. A complex consisting of TRAF6, TAK1 (TGFβ-activated kinase 1), and TAB (TAK1 binding protein) 1 and 2 goes on to activate the IκB kinase complex, resulting in nuclear factor (NF) κB translocation to the nucleus (Mercurio et al, 1997;Regnier et al, 1997;Jiang et al, 2003). CpG-induced NF-κB activation initiates the up-regulation of costimulatory molecules and the secretion of proinfl am matory cytokines, such as TNFα and IL-6.…”

Section: Introductionmentioning

confidence: 99%

CpG-induced tyrosine phosphorylation occurs via a TLR9-independent mechanism and is required for cytokine secretion

Sanjuán

Rao

Lai

et al. 2006

The Journal of Cell Biology

117

100

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Toll-like receptors (TLRs) recognize molecular patterns preferentially expressed by pathogens. In endosomes, TLR9 is activated by unmethylated bacterial DNA, resulting in proinflammatory cytokine secretion via the adaptor protein MyD88. We demonstrate that CpG oligonucleotides activate a TLR9-independent pathway initiated by two Src family kinases, Hck and Lyn, which trigger a tyrosine phosphorylation–mediated signaling cascade. This cascade induces actin cytoskeleton reorganization, resulting in cell spreading, adhesion, and motility. CpG-induced actin polymerization originates at the plasma membrane, rather than in endosomes. Chloroquine, an inhibitor of CpG-triggered cytokine secretion, blocked TLR9/MyD88-dependent cytokine secretion as expected but failed to inhibit CpG-induced Src family kinase activation and its dependent cellular responses. Knock down of Src family kinase expression or the use of specific kinase inhibitors blocked MyD88-dependent signaling and cytokine secretion, providing evidence that tyrosine phosphorylation is both CpG induced and an upstream requirement for the engagement of TLR9. The Src family pathway intersects the TLR9–MyD88 pathway by promoting the tyrosine phosphorylation of TLR9 and the recruitment of Syk to this receptor.

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Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFκB and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR

Cited by 6 publications

References 0 publications

An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells

An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells

Toll-Like Receptors and RNA Helicases: Two Parallel Ways to Trigger Antiviral Responses

CpG-induced tyrosine phosphorylation occurs via a TLR9-independent mechanism and is required for cytokine secretion

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