Activation of Acid Sphingomyelinase by Interleukin-1 (IL-1) Requires the IL-1 Receptor Accessory Protein

Hofmeister, Robert; Wiegmann, Katja; Korherr, Christian; Bernardo, Katussevani; Krönke, Martin; Falk, Werner

doi:10.1074/jbc.272.44.27730

Cited by 71 publications

(49 citation statements)

References 46 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The differential requirement of TR55 internalization for the activation of A-SMase and N-SMase are in concordance with a previous report by Hofmeister et al in which the authors used an independent approach to study the functional consequences of IL-1 receptor internalization (63). An IL-1 receptor type I-positive EL4 thymoma cell line was employed, which is defective in the IL-1R accessory protein (IL-1RAcP) required for IL-1 receptor internalization.…”

Section: Discussionsupporting

confidence: 68%

Inhibition of Receptor Internalization by Monodansylcadaverine Selectively Blocks p55 Tumor Necrosis Factor Receptor Death Domain Signaling

Schütze

Machleidt

Adam

et al. 1999

Journal of Biological Chemistry

Self Cite

191

142

View full text Add to dashboard Cite

The 55-kDa receptor for tumor necrosis factor (TR55) triggers multiple signaling cascades initiated by adapter proteins like TRADD and FAN. By use of the primary amine monodansylcadaverine (MDC), we addressed the functional role of tumor necrosis factor (TNF) receptor internalization for intracellular signal distribution. We show that MDC does not prevent the interaction of the p55 TNF receptor (TR55) with FAN and TRADD. Furthermore, the activation of plasmamembrane-associated neutral sphingomyelinase activation as well as the stimulation of proline-directed protein kinases were not affected in MDC-treated cells. In contrast, activation of signaling enzymes that are linked to the "death domain" of TR55, like acid sphingomyelinase and c-Jun-N-terminal protein kinase as well as TNF signaling of apoptosis in U937 and L929 cells, are blocked in the presence of MDC. The results of our study suggest a role of TR55 internalization for the activation of select TR55 death domain signaling pathways including those leading to apoptosis.Tumor necrosis factor (TNF), 1 originally defined by its antitumoral activity, is now recognized as a pleiotropic cytokine exerting a wide variety of immunoregulatory activities (for review, see Refs. 1-3). TNF action is mediated by two types of cell surface receptors of 55 kDa (TR55) and 75 kDa (TR75) molecular masses, respectively. Both receptors mediate distinct TNF responses (4 -6). The majority of activities of soluble TNF appears to be mediated by TR55 (7-11). Like other cytokine receptors, the cytoplasmic domain of both TNF receptors lacks intrinsic enzymatic activities. The activation of intracellular signaling enzyme systems is initiated by a selective interplay between the cytoplasmic domain of the TNF receptors and a number of recently identified TNF receptor-associated proteins (see Ref. Results from numerous studies have revealed that TNF signaling further involves activation of downstream enzyme systems at multiple subcellular compartments such as the plasmamembrane, endosomes, mitochondria, the cytosol, and the nucleus (for review, see Refs. 11, 23, and 24). Membrane-associated enzyme systems transmitting TR55 signals include plasmamembrane-bound phospholipases such as phosphatidylcholine-specific phospholipase C (25), which generates the lipid second messenger molecule 1,2-diacylglycerol and a N-SMase (9), producing ceramide by sphingomyelin hydrolysis. Ceramide generated at the plasmamembrane triggers activation of a 97-kDa ceramide-activated protein kinase (26), recently suggested to be identical with the "kinase suppressor of ras" (27). Ceramide-activated protein kinase belongs to a family of proline-directed protein kinases (PDPK) (9), including members of the mitogen-activated protein kinases (28). TNF signaling further involves intracellular membrane compartments like caveolae and endosomes harboring an acid SMase (A-SMase) (9,29,30). In mitochondria, TNF induces reactive oxygen species that are generated at the level of the oxidative phosphorylation complex III (31). T...

show abstract

Section: Discussionsupporting

confidence: 68%

Inhibition of Receptor Internalization by Monodansylcadaverine Selectively Blocks p55 Tumor Necrosis Factor Receptor Death Domain Signaling

Schütze

Machleidt

Adam

et al. 1999

Journal of Biological Chemistry

Self Cite

191

142

View full text Add to dashboard Cite

show abstract

“…The signaling IL-1 receptor complex consists of a heterodimer of IL-1RI that binds IL-1 and IL-1RAcP, which recognizes the ligated IL-1RI (4,5,18,20). The signaling IL-18 receptor complex also consists of a heterodimer in which the IL-18R␣-chain binds IL-18 (25) and the IL-18R␤-chain (26) functions as a coreceptor.…”

Section: Discussionmentioning

confidence: 99%

IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells

Ali

Huber

Kollewe³

et al. 2007

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

Self Cite

302

275

View full text Add to dashboard Cite

“…indeed several mediators known to increase the intracellular levels of ceramide are involved in the early immune response, i.e., TCR triggering, IL-1␤, TNF-␣, IFN-␥, and CD28 ligation (10,(12)(13)(14)(15)(32)(33)(34). When the T cell forms Ag-specific conjugates with APC, a supramolecular activation cluster is observed at the T-APC contact zone.…”

Section: Discussionmentioning

confidence: 99%

Ceramide-Induced TCR Up-Regulation

Menné

Lauritsen

Dietrich

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

The TCR is a constitutively recycling receptor meaning that a constant fraction of TCR from the plasma membrane is transported inside the cell at the same time as a constant fraction of TCR from the intracellular pool is transported to the plasma membrane. TCR recycling is affected by protein kinase C activity. Thus, an increase in protein kinase C activity affects TCR recycling kinetics leading to a new TCR equilibrium with a reduced level of TCR expressed at the T cell surface. Down-regulation of TCR expression compromises T cell activation. Conversely, TCR up-regulation is expected to increase T cell responsiveness. The purpose of this study was to identify and characterize potential pathways for TCR up-regulation. We found that ceramide affected TCR recycling dynamics and induced TCR up-regulation in a concentration- and time-dependent manner. Experiments applying phosphatase inhibitors indicated that ceramide-induced TCR up-regulation was most probably mediated by serine/threonine protein phosphatase 2A. Analyses of T cell variants demonstrated that TCR up-regulation was dependent on the presence of an intact CD3γ L-based motif and thus acted on TCR engaged in the recycling pathway. Finally, we showed that TCR up-regulation probably plays a physiological role by increasing T cell responsiveness. Thus, by affecting the TCR recycling kinetics, T cells have the potential both to up- and down-regulate TCR expression and thereby adjust T cell responsiveness.

show abstract

Activation of Acid Sphingomyelinase by Interleukin-1 (IL-1) Requires the IL-1 Receptor Accessory Protein

Abstract: The cytokine interleukin-1 (IL-1) plays an important role in inflammation and regulation of immune responses, but the mechanisms of its signal transduction and cell activation processes are incompletely understood. Ceramide generated by sphingomyelinases

Cited by 71 publications

References 46 publications

Inhibition of Receptor Internalization by Monodansylcadaverine Selectively Blocks p55 Tumor Necrosis Factor Receptor Death Domain Signaling

Inhibition of Receptor Internalization by Monodansylcadaverine Selectively Blocks p55 Tumor Necrosis Factor Receptor Death Domain Signaling

IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells

Ceramide-Induced TCR Up-Regulation

Contact Info

Product

Resources

About