The IL1 receptor accessory protein is responsible for the recruitment of the interleukin‐1 receptor associated kinase to the IL1/IL1 receptor I complex

Volpe, Filippo; Clatworthy, Jonathan; Kaptein, Allard; Maschera, Barbara; Griffin, Anne-Marie; Ray, Keith P.

doi:10.1016/s0014-5793(97)01426-9

Cited by 50 publications

(33 citation statements)

References 16 publications

(14 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The amplified sequence found was identical with that described previously (26). pFLAG-IL-1RAcP, which produces flag-tagged IL-1R accessory protein (27), was a gift from Dr. F. Volpe, Glaxo-Wellcome (Stevenage, U.K.). pCDM8-CD14 (28) was a gift from Prof. B.…”

Section: Cdna Preparationmentioning

confidence: 69%

“…To investigate the mechanism of the observed TLR1-TLR2 cooperation, TLR2 was cotransfected with vectors directing expression of TLR1, TLR1⌬cyt, or the accessory chain of the IL-1R (IL1RAcP) (27), which contains a TIR signaling domain related to those of TLRs (3). We reasoned that if the increase in signaling was a nonspecific effect due to increased expression of TIR domains, then IL-1RAcP might substitute for TLR1.…”

Section: Full-length Tlr1 Is Required For Tlr2-dependent Responses Tomentioning

confidence: 99%

See 1 more Smart Citation

Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses

Wyllie

Kiss-Tóth

Visintin

et al. 2000

The Journal of Immunology

245

151

View full text Add to dashboard Cite

Members of the Toll-like receptor (TLR) family are components of the mammalian anti-microbial response, signaling with a domain closely related to that of IL-1 receptors. In this report the expression and function of TLR1, a TLR of unknown function, are examined. TLR1 is expressed by monocytes, as demonstrated using a novel mAb. Monocytes also express TLR2. TLR1 transfection of HeLa cells, which express neither TLR1 nor TLR2, was not sufficient to confer responsiveness to several microbial extracts. However, cotransfection of TLR1 and TLR2 resulted in enhanced signaling by HeLa cells to soluble factors released from Neisseria meningitidis relative to the response with either TLR alone. This phenomenon was also seen with high concentrations of some preparations of LPS. The N. meningitidis factors recognized by TLR1/TLR2 were not released by N. meningitidis mutant in the LpxA gene. Although LpxA is required for LPS biosynthesis, because cooperation between TLR1 and TLR2 was not seen with all LPS preparations, the microbial component(s) TLR1/2 recognizes is likely to be a complex of LPS and other molecules or a compound metabolically and chemically related to LPS. The functional IL-1R consists of a heterodimer; this report suggests a similar mechanism for TLR1 and TLR2, for certain agonists. These data further suggest that mammalian responsiveness to some bacterial products may be mediated by combinations of TLRs, suggesting a mechanism for diversifying the repertoire of Toll-mediated responses.

show abstract

Section: Cdna Preparationmentioning

confidence: 69%

Section: Full-length Tlr1 Is Required For Tlr2-dependent Responses Tomentioning

confidence: 99%

Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses

Wyllie

Kiss-Tóth

Visintin

et al. 2000

The Journal of Immunology

245

151

View full text Add to dashboard Cite

show abstract

“…Although previous studies have shown that the IL-1 receptors localize to focal contact sites in human fibroblasts and keratinocytes (41)(42)(43) and that IRAK and IL-1R I associate in IL-1-stimulated cells (45), a physical association between IRAK, IL-1R 1 , and focal adhesions has not been established. We first determined by immunoblot analysis that IL-1R 1 could be detected in beadassociated complexes at 10 and 20 min following the addition of collagen-coated microbeads to fibroblasts (Fig.…”

Section: Irak Recruitment Into Nascent Facs Requires Il-1-facsmentioning

confidence: 95%

The Recruitment of the Interleukin-1 (IL-1) Receptor-associated Kinase (IRAK) into Focal Adhesion Complexes Is Required for IL-1β-induced ERK Activation

MacGillivray¹,

Cruz²,

McCulloch³

2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…IL1RAP is an essential component of the IL-1 coreceptor complex required for IL-1β-induced signaling (8)(9)(10). Coexpression of IL1RAP and IL-1RI can mimic IL-1β stimulation for activation of NF-κB (Fig.…”

Section: Identification Of March8 As a Negative Regulator Of Il-1β-inmentioning

confidence: 99%

“…IL-1RI is the ligand-recognition receptor that binds IL-1β directly (7). Although IL1RAP does not bind IL-1β directly, its recruitment to IL-1RI following IL-1β stimulation is essential for the formation of an activated membrane receptor complex (8)(9)(10)). The activated complex can then recruit intracellular adaptor proteins and kinases, including MyD88, IRAK4, and IRAK1 (11)(12)(13)(14).…”

mentioning

confidence: 99%

The E3 ubiquitin ligase MARCH8 negatively regulates IL-1β-induced NF-κB activation by targeting the IL1RAP coreceptor for ubiquitination and degradation

Chen

Zhang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

104

View full text Add to dashboard Cite

The proinflammatory cytokine interleukin-1 (IL-1) signals via type I IL-1 receptor (IL-1RI) and IL-1 receptor accessory protein (IL1RAP), which leads to activation of the transcription factor NF-κB and induction of a range of downstream proteins involved in inflammatory and immune responses. Here, we identified the E3 ubiquitin ligase membrane-associated RING-CH (MARCH8) as a suppressor of IL-1β-induced NF-κB-and MAPK-activation pathways. Overexpression of MARCH8 inhibits IL-1β-induced NF-κB and MAPK activation, whereas knockdown of MARCH8 has the opposite effect. Mechanistically, MARCH8 interacts with IL1RAP and targets its Lys512 for K48-linked polyubiquitination and degradation. Our findings suggest that MARCH8-mediated polyubiquitination and degradation of IL1RAP is an important mechanism for negative regulation of IL-1β-induced signaling pathways.T he transcription factor NF-κB plays pivotal roles in many aspects of cellular processes such as inflammation, innate immunity, and cancer. NF-κB is sequestered in the cytoplasm and kept inactive in nonstimulated cells by binding to inhibitory IκB (inhibitor of κB) proteins. Under stimulation with cytokines, infectious pathogens, or genotoxic stresses, the IκB proteins are phosphorylated, ubiquitinated, and ultimately degraded, which frees NF-κB for translocation into the nucleus, where it induces transcription of downstream target genes (1-3).Interleukin 1 (IL-1) is a critical proinflammatory cytokine that can trigger a cascade of signaling leading to activation of NF-κB. It functions through engagement of two membrane-bound receptors: IL-1 receptor type I (IL-1RI) and IL-1 receptor accessory protein (IL1RAP) (4-6). IL-1RI is the ligand-recognition receptor that binds IL-1β directly (7). Although IL1RAP does not bind IL-1β directly, its recruitment to IL-1RI following IL-1β stimulation is essential for the formation of an activated membrane receptor complex (8-10). The activated complex can then recruit intracellular adaptor proteins and kinases, including MyD88, IRAK4,. IRAK4 phosphorylates and activates IRAK1, which in turn recruits TRAF6. IRAK1 and TRAF6 form a complex that is released from the receptor complex (15, 16). TRAF6 possesses an E3 ubiquitin ligase activity that mediates its autoubiquitination. Ubiquitinated TRAF6 further recruits the TGF-b-activated kinase 1 (TAK1)-TAK1-binding protein 2 (TAB2)-TAB3 complex, resulting in the activation of TAK1. Activated TAK1 subsequently activates downstream kinases IKK-α and IKK-β, which phosphorylate IκB proteins, and lead to activation of NF-κB (17).Several studies have suggested that ubiquitination is a central rhythm of regulation of IL-1β-induced NF-κB activation pathways. It has been shown that the E3 ubiquitin ligase TRAF6 mediates K63-linked polyubiquitination of IRAK1 for recruiting IKK and activating NF-κB (18). Tripartite motif 8 (TRIM8) catalyzes K63-linked polyubiquitination of TAK1, and this promotes the activation of TAK1 (19). It has also been demonstrated that the E3 ligase Pellino 3b acts as a n...

show abstract

The IL1 receptor accessory protein is responsible for the recruitment of the interleukin‐1 receptor associated kinase to the IL1/IL1 receptor I complex

Cited by 50 publications

References 16 publications

Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses

Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses

The Recruitment of the Interleukin-1 (IL-1) Receptor-associated Kinase (IRAK) into Focal Adhesion Complexes Is Required for IL-1β-induced ERK Activation

The E3 ubiquitin ligase MARCH8 negatively regulates IL-1β-induced NF-κB activation by targeting the IL1RAP coreceptor for ubiquitination and degradation

Contact Info

Product

Resources

About