Signal transduction by a protease cascade

LeMosy, Ellen K.; Hong, Charles C.; Hashimoto, Carl

doi:10.1016/s0962-8924(98)01494-9

Cited by 110 publications

(74 citation statements)

References 36 publications

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“…Invading pathogens are recognized by specific motifs or pathogen-associated molecular patterns (PAMPs) through different TLRs (Iwasaki and Medzhitov, 2004;Kaisho and Akira, 2004;Takeda and Akira, 2005). The Toll receptor was originally identified in Drosophila as a receptor essential for the establishment of a dorsal-ventral pattern (Lemosy et al, 1998;Minakhina and Steward, 2006). Subsequently, multiple homologs of the Toll receptor were identified in mammals and the TLR family now consists of 13 members (10 in humans), which are expressed differentially among immune and non-immune cells and respond to different components of invading pathogens (Ulevitch, 2000).…”

Section: Tlr-dependent Signaling To Nf-jb and The Innate Immune Responsementioning

confidence: 99%

Manipulation of the nuclear factor-κB pathway and the innate immune response by viruses

et al. 2006

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Section: Tlr-dependent Signaling To Nf-jb and The Innate Immune Responsementioning

confidence: 99%

Manipulation of the nuclear factor-κB pathway and the innate immune response by viruses

et al. 2006

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“…To elucidate whether these inhibitors act upstream or proteases (the products of the nudel, gastrulationdefective, snake and easter genes) (LeMosy et al, 1999). To date, no proteolytic event has been demonstrated upstream of the receptor in mammalian TLR.…”

Section: Proteases Involved In Lps Signalling Act Downstream Of Tlr4mentioning

confidence: 99%

TLR4-dependent lipopolysaccharide signalling in epithelial cells is independent of extracellular protease activity

2002

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Summary Epithelial cells are the first cells that encounter infecting bacteria and, as such, they have developed several mechanisms for microbial protection. We have shown previously that bladder epithelial cells express the lipopolysaccharide (LPS) receptor Toll‐like receptor (TLR) 4 that enables a rapid cellular interleukin (IL)‐8 response when exposed to Escherichia coli and LPS. TLR4 belongs to a family of receptors that was initially identified in Drosophila, in which Toll is required for the immune response against fungi. Fungal exposure activates a series of serine proteases that process the protein Spaetzle to a cytokine‐like form that acts as a ligand for Toll. Here, we investigated whether a similar proteolytic cascade is required for human TLR activation. When screening a set of 18 protease inhibitors, three serine protease inhibitors (TPCK, TLCK and Pefabloc) were shown to inhibit LPS‐ and peptidoglycan‐induced IL‐8 production in TLR2‐ and TLR4‐positive bladder epithelial cells. However, they were equally effective inhibitors of IL‐1β‐induced signalling, indicating that their target(s) is/are located downstream of the TLRs. Further characterization showed that these inhibitors blocked IκB degradation but not phosphorylation in LPS‐stimulated cells, which suggests that the serine protease inhibitors target the 26S proteasome. Identical results were obtained on LPS‐stimulated monocytes. Based on these data, we find no evidence for the involvement of proteases upstream of TLRs in either epithelial cells or cells of the monocytic lineage.

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“…Two of these gradients, responsible for the dorsoventral and terminal patterning, are established by cascades of reaction-diffusion modules (11). The dorsoventral gradient depends on a cascade of extracellular proteolysis reactions, similar to the ones characterized in the blood clotting system (13,14). The transcriptional response to this gradient has been extensively studied, but the gradient itself is yet to be quantified (15,16).…”

mentioning

confidence: 99%