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PMID: 17890055 IL-1 induces a wide variety of inflammatory mediators including IL-6 and tumor necrosis factor (TNF) alpha.

indirect

indirect

PMID: 17890055 IL-1 induces a wide variety of inflammatory mediators including IL-6 and tumor necrosis factor (TNF) alpha.

indirect

indirect

PMID: 17890055 IL-1 induces a wide variety of inflammatory mediators including IL-6 and tumor necrosis factor (TNF) alpha.

PMID: 17890055,16286016 IL-33-treatment of Th2 T cells induces IL-5 and IL-13 production

indirect

indirect

PMID: 17890055,16286016 IL-33-treatment of Th2 T cells induces IL-5 and IL-13 production

indirect

indirect

PMID: 17890055,16286016 IL-33-treatment of Th2 T cells induces IL-5 and IL-13 production

indirect

indirect

indirect

PMID: 17890055,15767370 IFN-alpha production induced by intravenous injection of TLR7 agonists is completely blocked in IRAK1-deficient mice but IL-12 production remains normal PMID: 17890055,15767370 IRAK1 deficiency in plasmacytoid dendritic cells abrogates IFN-alpha production without affecting the production of other inflammatory cytokines such as IL-6 and TNF-alpha

PMID: 17890055,15767370 IFN-alpha production induced by intravenous injection of TLR7 agonists is completely blocked in IRAK1-deficient mice but IL-12 production remains normal PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

indirect

indirect

PMID: 17890055,12626533 However, another study using splenocytes from IRAK1-deficient animals reported a significant reduction in TNF-alpha and IL-12 upon TLR9 activation

PMID: 17890055,15767370 IFN-alpha production induced by intravenous injection of TLR7 agonists is completely blocked in IRAK1-deficient mice but IL-12 production remains normal PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

indirect

indirect

PMID: 17890055,12626533 However, another study using splenocytes from IRAK1-deficient animals reported a significant reduction in TNF-alpha and IL-12 upon TLR9 activation

indirect

indirect

indirect

PMID: 17890055 Together, these results suggest that IRAK1 plays a specific and essential role in IFN-alpha induction downstream of TLR7 and TLR9

PMID: 17890055,10854325,16428431 Prior to receptor activation, IRAK1 is associated with Tollip in the cytosol

PMID: 17890055 Upon ligand binding to TLR/IL-1R, myeloid differentiation factor 88 (MyD88) is rapidly recruited to the receptor via interaction of Toll/IL-1R (TIR) domains which are present in both MyD88 and TLR/IL-1R.

PMID: 17890055 Upon ligand binding to TLR/IL-1R, myeloid differentiation factor 88 (MyD88) is rapidly recruited to the receptor via interaction of Toll/IL-1R (TIR) domains which are present in both MyD88 and TLR/IL-1R.

PMID: 17890055 Upon ligand binding to TLR/IL-1R, myeloid differentiation factor 88 (MyD88) is rapidly recruited to the receptor via interaction of Toll/IL-1R (TIR) domains which are present in both MyD88 and TLR/IL-1R.

PMID: 17890055,9430229,17276401 IRAK1 is also recruited to the receptor complex through a death domain interaction with MyD88

PMID: 17890055,9430229,17276401 IRAK1 is also recruited to the receptor complex through a death domain interaction with MyD88

PMID: 17890055,11960013 ,12538665 Binding to MyD88 brings IRAK1 and IRAK4 together at the receptor complex and facilitates the phosphorylation of IRAK1 by IRAK4 at Thr-209 and Thr-387

PMID: 17890055,11960013 ,12538665 Binding to MyD88 brings IRAK1 and IRAK4 together at the receptor complex and facilitates the phosphorylation of IRAK1 by IRAK4 at Thr-209 and Thr-387

PMID: 17890055,11287640 IRAK1 also binds tumor necrosis factor receptor-associated factor 6 (TRAF6) through multiple regions including the death domain, the undefined domain and the C-terminal C1 domain PMID: 17890055 IRAK1 also interacts with TRAF6

PMID: 17890055,11287640 IRAK1 also binds tumor necrosis factor receptor-associated factor 6 (TRAF6) through multiple regions including the death domain, the undefined domain and the C-terminal C1 domain PMID: 17890055 IRAK1 also interacts with TRAF6

PMID: 17890055,11960013 ,12538665 Binding to MyD88 brings IRAK1 and IRAK4 together at the receptor complex and facilitates the phosphorylation of IRAK1 by IRAK4 at Thr-209 and Thr-387

PMID: 17890055,11960013 ,12538665 Binding to MyD88 brings IRAK1 and IRAK4 together at the receptor complex and facilitates the phosphorylation of IRAK1 by IRAK4 at Thr-209 and Thr-387

PMID: 17890055,8599092,17141195 This results in the activation of IRAK1 kinase activity and thus the formation of hyper-phosphorylated IRAK1 via auto-phosphorylation

PMID: 17890055,8599092,17141195 This results in the activation of IRAK1 kinase activity and thus the formation of hyper-phosphorylated IRAK1 via auto-phosphorylation

PMID: 17890055,9430229 Since MyD88 and Tollip only bind to non-phosphorylated IRAK1, hyper-phosphorylated IRAK1 is then released from MyD88 and the receptor complex, a key step in this signaling cascade PMID: 17890055 Hyper-phosphorylated IRAK1 then disengages from MyD88 and Tollip, and forms a cytosolic IRAK1-TRAF6 complex

PMID: 17890055,9430229 Since MyD88 and Tollip only bind to non-phosphorylated IRAK1, hyper-phosphorylated IRAK1 is then released from MyD88 and the receptor complex, a key step in this signaling cascade PMID: 17890055 Hyper-phosphorylated IRAK1 then disengages from MyD88 and Tollip, and forms a cytosolic IRAK1-TRAF6 complex

PMID: 17890055,12496252 An intermediate cytosolic signaling complex composed of Pellino1, IRAK1, IRAK4 and TRAF6 may be formed prior to the interaction of TRAF6 with the downstream signaling molecule TGF-beta activated kinase-1 (TAK1)

PMID: 17890055,12496252 An intermediate cytosolic signaling complex composed of Pellino1, IRAK1, IRAK4 and TRAF6 may be formed prior to the interaction of TRAF6 with the downstream signaling molecule TGF-beta activated kinase-1 (TAK1)

PMID: 17890055,10882101,12242293,11057907 Cytosolic TRAF6 interacting with TAK1 eventually forms a macromolecular complex with ubiquitin conjugating enzymes Ubc13 and Uev1A, and TAK1 binding proteins TAB1 and TAB2

indirect

PMID: 17890055,11518704,10465784 This leads to TAK1 activation, which in turn activates NF-κB and MAPK pathways

indirect

PMID: 17890055,11518704,10465784 This leads to TAK1 activation, which in turn activates NF-κB and MAPK pathways

indirect

PMID: 17890055,11518704,10465784 This leads to TAK1 activation, which in turn activates NF-κB and MAPK pathways

indirect

PMID: 17890055,11518704,10465784 This leads to TAK1 activation, which in turn activates NF-κB and MAPK pathways

PMID: 17890055,10899313,15896328 IRAK1 has been reported to translocate to the nucleus upon IL-1 stimulation PMID: 17890055,16690127 A recent study also indicated that IRAK1 undergoes sumoylation followed by nuclear translocation in monocytes stimulated with TLR ligands

PMID: 17890055,16690127 A recent study also indicated that IRAK1 undergoes sumoylation followed by nuclear translocation in monocytes stimulated with TLR ligands

indirect

PMID: 17890055,15465816 Within the nucleus, IRAK1 has been reported to phosphorylate transcription factor Stat3 and bind directly to the IL-10 gene promoter for IL-10 expression

indirect

PMID: 17890055,15465816 Within the nucleus, IRAK1 has been reported to phosphorylate transcription factor Stat3 and bind directly to the IL-10 gene promoter for IL-10 expression

PMID: 17890055,15465816 Within the nucleus, IRAK1 has been reported to phosphorylate transcription factor Stat3 and bind directly to the IL-10 gene promoter for IL-10 expression

PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

indirect

PMID: 17890055,9261174 The loss of IRAK1 protein is due to proteasome-mediated degradation as demonstrated by studies using proteasome inhibitors PMID: 17890055,11937546 TLR4 activation can also trigger rapid IRAK1 degradation that can be blocked by protein kinase C (PKC) specific inhibitors PMID: 17890055,12032143 Interestingly, degradation of IRAK1 in LPS-tolerant THP-1 cells can be prevented by pretreatment with GM-CSF and IFN-γ

PMID: 17890055,11937546 TLR4 activation can also trigger rapid IRAK1 degradation that can be blocked by protein kinase C (PKC) specific inhibitors

PMID: 17890055 In resting cells, IRAK1c dimerizes with IRAK1 or IRAK2 and associates with Tollip.

PMID: 17890055 n resting cells, IRAK1c dimerizes with IRAK1 or IRAK2 and associates with Tollip.

PMID: 17890055 In resting cells, IRAK1c dimerizes with IRAK1 or IRAK2 and associates with Tollip.

PMID: 17890055 In resting cells, IRAK1c dimerizes with IRAK1 or IRAK2 and associates with Tollip.

PMID: 17890055 Upon TLR activation, IRAK1c is recruited to the receptor complex and interacts with MyD88 and TRAF6 in a manner similar to IRAK1 and IRAK1-kinase dead mutant.

PMID: 17890055 Upon TLR activation, IRAK1c is recruited to the receptor complex and interacts with MyD88 and TRAF6 in a manner similar to IRAK1 and IRAK1-kinase dead mutant.

PMID: 17890055 Upon TLR activation, IRAK1c is recruited to the receptor complex and interacts with MyD88 and TRAF6 in a manner similar to IRAK1 and IRAK1-kinase dead mutant.

PMID: 17890055 Upon TLR activation, IRAK1c is recruited to the receptor complex and interacts with MyD88 and TRAF6 in a manner similar to IRAK1 and IRAK1-kinase dead mutant.

PMID: 17890055,12032143 Interestingly, degradation of IRAK1 in LPS-tolerant THP-1 cells can be prevented by pretreatment with GM-CSF and IFN-γ

PMID: 17890055,12032143 Interestingly, degradation of IRAK1 in LPS-tolerant THP-1 cells can be prevented by pretreatment with GM-CSF and IFN-γ

PMID: 17890055,16831874 IRAK1 also acts as an upstream adaptor by recruiting B-cell CLL/lymphoma 10 (BCL10) to the TLR signaling complex

PMID: 17890055 Further biochemical studies showed that IFN-alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

PMID: 17890055 Further biochemical studies showed that IFN-alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

PMID: 17890055 Further biochemical studies showed that IFN-alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

indirect

PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7)

PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

PMID: 17890055 Further biochemical studies showed that IFN-greek small letter alpha induction requires the formation of a signaling complex consisting of IRAK1, MyD88, TRAF6 and IFN-regulatory factor 7 (IRF7) PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.

PMID: 17890055,15767370 IRAK1 directly binds IRF7 and its kinase activity is critical for the phosphorylation and activation of IRF7, a requirement for IRF7 nuclear translocation and INF-alpha production PMID: 17890055 As previously mentioned, IRAK1 plays a key role in IFN-alpha gene expression upon TLR7 or TLR9 activation.