Differential Regulation of TNF-R1 Signaling: Lipid Raft Dependency of p42mapk/erk2 Activation, but Not NF-κB Activation

Doan, Joyce E. S.; Windmiller, David A.; Riches, David W. H.

doi:10.4049/jimmunol.172.12.7654

Cited by 53 publications

(57 citation statements)

References 41 publications

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“…Our studies show that TBI induced a rapid transient activation of NF-B, but the signaling molecules involved in NF-B activation were mostly excluded from lipid rafts in cerebral cortices of naive and injured animals. These findings are in agreement with results of a recent study in primary macrophage cultures that demonstrated that I-B kinase-␥ and I-B-␣ are excluded from raftcontaining fractions after TNF-␣ stimulation (Doan et al, 2004) but differ from results in the fibrosarcoma cell line, HT-1080, in which NF-B signaling intermediates were present in lipid rafts and TNF-␣-induced activation of NF-B was blocked by cholesterol depletion (Legler et al, 2003). Because TNFR1 is localized to lipid rafts and nonraft regions of the plasma membrane, each compartment may be capable of initiating different signaling responses.…”

Section: Discussionsupporting

confidence: 83%

“…These observations are in agreement with partitioning of TNFR1 in lipid rafts of fibroblasts (Veldman et al, 2001), human fibrosarcoma cells (Legler et al, 2003), and primary cultures of mouse macrophages (Doan et al, 2004) after TNF-␣ activation. RIP and cIAP-1 dissociate from TNFR1, whereas FADD and cIAP-2 increase association with this receptor-signaling complex in lipid rafts.…”

Section: Discussionsupporting

confidence: 78%

“…Recent in vitro evidence suggests that redistribution of TNFR1 into specialized microdomains (lipid rafts) may account for the outcome of some TNF-␣-activated signaling pathways (Cottin et al, 2002;Legler et al, 2003), but TNFR1 localized to nonraft regions of the plasma membrane are capable of initiating different signaling responses (Doan et al, 2004); however, the role of microdomains in signal transduction emanating from the TNFR family in vivo has not been addressed. Here we show that TNFR1 is present in lipid rafts in normal rat cerebral cortex.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tumor Necrosis Factor Receptor 1 and Its Signaling Intermediates Are Recruited to Lipid Rafts in the Traumatized Brain

Lotocki¹,

Alonso

Dietrich³

et al. 2004

J. Neurosci.

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The tumor necrosis factor (TNF) ligand-receptor system plays an essential role in apoptosis that contributes to secondary damage after traumatic brain injury (TBI). TNF also stimulates inflammation by activation of gene transcription through the IB kinase (IKK)/NF-B and JNK (c-Jun N-terminal protein kinase)/AP-1 signaling cascades. The mechanism by which TNF signals between cell death and survival and the role of receptor localization in the activation of downstream signaling events are not fully understood. Here, TNF receptor 1 (TNFR1) signaling complexes in lipid rafts were investigated in the cerebral cortex of adult male Sprague Dawley rats subjected to moderate (1.8 -2.2 atmospheres) fluid-percussion TBI and naive controls. In the normal rat cortex, a portion of TNFR1 was present in lipid raft microdomains, where it associated with the adaptor proteins TRADD (TNF receptor-associated death domain), TNF receptorassociated factor-2 (TRAF-2), the Ser/Thr kinase RIP (receptor-interacting protein), TRAF1, and cIAP-1 (cellular inhibitor of apoptosis protein-1), forming a survival signaling complex. Moderate TBI resulted in rapid recruitment of TNFR1, but not TNFR2 or Fas, to lipid rafts and induced alterations in the composition of signaling intermediates. TNFR1 and TRAF1 were polyubiquitinated in lipid rafts after TBI. Subsequently, the signaling complex contained activated caspase-8, thus initiating apoptosis. In addition, TBI caused a transient activation of NF-B, but receptor signaling interacting proteins IKK␣ and IKK␤ were not detected in raft-containing fractions. Thus, redistribution of TNFR1 in lipid rafts and nonraft regions of the plasma membrane may regulate the diversity of signaling responses initiated by these receptors in the normal brain and after TBI.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

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Tumor Necrosis Factor Receptor 1 and Its Signaling Intermediates Are Recruited to Lipid Rafts in the Traumatized Brain

Lotocki¹,

Alonso

Dietrich³

et al. 2004

J. Neurosci.

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“…Hybrid-type N-glycans contain two a-1,3/6-linked terminal mannose residues, as well as one N-acetyllactosamine branch. It is tempting to speculate that at least one of these carbohydrate structures is involved in the spatial compartmentalization of receptors between lipid raft and nonraft regions of the plasma membrane (43), which was shown to be critical for the diversity of signaling responses initiated by TNF-R1 (44). In contrast, an unusual (high-mannose) carbohydrate moiety attached to the receptor could directly induce conformational changes that disable TNF-R1 signaling without affecting ligand binding (45).…”

Section: Discussionmentioning

confidence: 99%

Control of TNF-Induced Dendritic Cell Maturation by Hybrid-Type N-Glycans

Schlickeiser

Stanojlović²,

Appelt

et al. 2011

The Journal of Immunology

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The activity of α-1,2-mannosidase I is required for the conversion of high-mannose to hybrid-type (ConA reactive) and complex-type N-glycans (Phaseolus vulgaris-leukoagglutinin [PHA-L] reactive) during posttranslational protein N-glycosylation. We recently demonstrated that α-1,2-mannosidase I mRNA decreases in graft-infiltrating CD11c+ dendritic cells (DCs) prior to allograft rejection. Although highly expressed in immature DCs, little is known about its role in DC functions. In this study, analysis of surface complex-type N-glycan expression by lectin staining revealed the existence of PHA-Llow and PHA-Lhigh subpopulations in murine splenic conventional DCs, as well as in bone marrow-derived DC (BMDCs), whereas plasmacytoid DCs are nearly exclusively PHA-Lhigh. Interestingly, all PHA-Lhigh DCs displayed a strongly reduced responsiveness to TNF-α–induced p38-MAPK activation compared with PHA-Llow DCs, indicating differences in PHA-L–binding capacities between DCs with different inflammatory properties. However, p38 phosphorylation levels were increased in BMDCs overexpressing α-1,2-mannosidase I mRNA. Moreover, hybrid-type, but not complex-type, N-glycans are required for TNF-α–induced p38-MAPK activation and subsequent phenotypic maturation of BMDCs (MHC-II, CD86, CCR7 upregulation). α-1,2-mannosidase I inhibitor-treated DCs displayed diminished transendothelial migration in response to CCL19, homing to regional lymph nodes, and priming of IFN-γ–producing T cells in vivo. In contrast, the activity of α-1,2-mannosidase I is dispensable for LPS-induced signaling, as well as the DCs’ general capability for phenotypic and functional maturation. Systemic application of an α-1,2-mannosidase I inhibitor was able to significantly prolong allograft survival in a murine high-responder corneal transplantation model, further highlighting the importance of N-glycan processing by α-1,2-mannosidase I for alloantigen presentation and T cell priming.

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“…For example, downregulation of p55 TNFR by phosphorylation has been shown to selectively decrease MAPK activation in the presence of preserved NF-B function (56). In contrast, preferential activation of MAPK but not NF-B has been reported to be determined by the location of the p55 TNFR in lipid or nonlipid raft components of the plasma membrane (57). Upon activation by TNF, p55 TNFR is segregated to predominantly lipid rafts in the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Regulation of IL-1 and TNF Receptor Expression and Function by Endogenous Macrophage Migration Inhibitory Factor

Toh

Aeberli

Lacey

et al. 2006

The Journal of Immunology

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Macrophage migration inhibitory factor (MIF) has a key role in regulation of innate and adaptive immunity and is implicated in sepsis, tumorigenesis, and autoimmune disease. MIF deficiency or immunoneutralization leads to protection against fatal endotoxic, exotoxic, and infective shock, and anti-inflammatory effects in other experimental models of inflammatory disease. We report a novel regulatory role of MIF in type 1 IL-1R and p55 TNFR expression and function. Compared with wild-type cells, MIF-deficient cells were hyporesponsive to IL-1- and TNF-induced MAPK activity, AP-1 activity, and cellular proliferation, while NF-κB function was preserved. Hyporesponsiveness of MIF-deficient cells was associated with down-regulation of cytokine receptor expression, which was restored by reconstitution of either an upstream kinase of MAPK, MAPK/ERK kinase, or MIF. These data suggest that endogenous MIF is required for cytokine activation of MAPK/AP-1 and cytokine receptor expression. This autocrine regulatory pathway defines an important amplifying role of endogenous MIF in cytokine-mediated immune and inflammatory diseases and provides further molecular evidence for the critical role of MIF in cellular activation.

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Differential Regulation of TNF-R1 Signaling: Lipid Raft Dependency of p42mapk/erk2 Activation, but Not NF-κB Activation

Cited by 53 publications

References 41 publications

Tumor Necrosis Factor Receptor 1 and Its Signaling Intermediates Are Recruited to Lipid Rafts in the Traumatized Brain

Tumor Necrosis Factor Receptor 1 and Its Signaling Intermediates Are Recruited to Lipid Rafts in the Traumatized Brain

Control of TNF-Induced Dendritic Cell Maturation by Hybrid-Type N-Glycans

Regulation of IL-1 and TNF Receptor Expression and Function by Endogenous Macrophage Migration Inhibitory Factor

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