Lipid rafts: cell surface platforms for T cell signaling

Magee, Tony; Pirinen, Niina; Adler, Jeremy; Pagakis, Stamatis N.; Parmryd, Ingela

doi:10.4067/s0716-97602002000200003

Cited by 86 publications

(65 citation statements)

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“…Here, together with sterols, they form the microdomains known as lipid rafts (Futerman and Hannun 2004). Such domains have been suggested to be central to a wide array of cellular processes, including the formation of signal transduction complexes (Magee, et al 2002;Pierce 2002) and the polarized trafficking of lipid-modified proteins (Brown and London 1998). Importantly, sphingolipid metabolites such as ceramide and phosphorylated sphingosine (sphingosine-1-phosphate), are also involved in the intracellular signal transduction processes that regulate cell growth, differentiation and programmed cell death (apoptosis) (Futerman and Hannun 2004).…”

Section: Introductionmentioning

confidence: 99%

A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase

Mina

Mosely

Ali

et al. 2010

The International Journal of Biochemistry & Cell Biology

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P.W. (2010) 'A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase.', International journal of biochemistry and cell biology., 42 (9). pp. 1553-1561. Further information on publisher's website:https://doi.org/10. 1016/j.biocel.2010.06.008 Publisher's copyright statement: NOTICE: this is the author's version of a work that was accepted for publication in International journal of biochemistry and cell biology. Additional information:Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. N-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl) Furthermore, inhibitory substrate analogues have been identified. Importantly this assay is amenable to development for use in high-throughput screening applications for lead inhibitors and as such may prove to be a pivotal tool in drug discovery.3

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Section: Introductionmentioning

confidence: 99%

A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase

Mina

Mosely

Ali

et al. 2010

The International Journal of Biochemistry & Cell Biology

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“…), and bulk splenocytes (E:T cell ratio, 50:1) were used after RBC lysis in Trisammonium chloride for 2 min. After 4 h of incubation at 37°C, released 51 Cr was determined, and specific lysis was calculated as: 100 ϫ ((experimental Ϫ spontaneous release)/(total Ϫ spontaneous release)). For bystander killing, the same experiment was performed using unsensitized P815 cells, and CTL were pretreated with 30 M brefeldin A for 2 h at 37°C.…”

Section: Cytotoxic Assaysmentioning

confidence: 99%

“…For in vitro cytotoxicity assay, 51 Cr-labeled P815 cells (5 ϫ 10 3 cells/well) transfected, or not, with D b or K b (35) were incubated in DMEM supplemented with 5% FCS in 96-well microtiter plates for 30 min at 37°C with the indicated concentrations of IASA-YIPSAEK(ABA)I, F(N3)-AVYNFATA, or KAVYNFATA peptide. In the case of the IASA-YIPSAEK(ABA)I peptide, the cells were irradiated at Ն350 nm (34); in the case of the F(N3)-AVYNFATA peptide, they were irradiated at 312 Ϯ 40 nM.…”

Section: Cytotoxic Assaysmentioning

confidence: 99%

Soluble MHC-Peptide Complexes Containing Long Rigid Linkers Abolish CTL-Mediated Cytotoxicity

Angelov

Guillaume

Cebecauer

et al. 2006

The Journal of Immunology

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Soluble MHC-peptide (pMHC) complexes induce intracellular calcium mobilization, diverse phosphorylation events, and death of CD8+ CTL, given that they are at least dimeric and coengage CD8. By testing dimeric, tetrameric, and octameric pMHC complexes containing spacers of different lengths, we show that their ability to activate CTL decreases as the distance between their subunit MHC complexes increases. Remarkably, pMHC complexes containing long rigid polyproline spacers (≥80 Å) inhibit target cell killing by cloned S14 CTL in a dose- and valence-dependent manner. Long octameric pMHC complexes abolished target cell lysis, even very strong lysis, at nanomolar concentrations. By contrast, an altered peptide ligand antagonist was only weakly inhibitory and only at high concentrations. Long Db-gp33 complexes strongly and specifically inhibited the Db-restricted lymphocytic choriomeningitis virus CTL response in vitro and in vivo. We show that complications related to transfer of peptide from soluble to cell-associated MHC molecules can be circumvented by using covalent pMHC complexes. Long pMHC complexes efficiently inhibited CTL target cell conjugate formation by interfering with TCR-mediated activation of LFA-1. Such reagents provide a new and powerful means to inhibit Ag-specific CTL responses and hence should be useful to blunt autoimmune disorders such as diabetes type I.

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“…For example, the unmodified sphingolipid ceramide acts as a secondary signalling molecule [3] and more complex species are implicated in the formation and function of signal transduction complexes [4,5]. The primary phosphosphingolipid species in mammalian species, including humans, is sphingomyelin (SM).…”

Section: Introductionmentioning

confidence: 99%

The Trypanosoma brucei sphingolipid synthase, an essential enzyme and drug target

Mina

Pan

Wansadhipathi

et al. 2009

Molecular and Biochemical Parasitology

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Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractSphingolipids are important components of eukaryotic membranes, particularly the plasma membrane, and are involved in a diverse array of signal transduction processes.In the Eukaryota the biosynthetic pathway for the formation of these lipid species is largely conserved. However, in contrast to mammals which produce sphingomyelin (SM), several pathogenic fungi and protozoa synthesize inositol phosphorylceramide 3 Key wordsTrypanosoma, trypanosomiasis, sphingolipid synthase, drug target FootnoteSince the initial submission of this work to Molecular and Biochemical Parasitology a paper has been published in Molecular Microbiology identifying and characterising the same family of enzymes in Trypanosoma brucei:

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Lipid rafts: cell surface platforms for T cell signaling

Cited by 86 publications

References 0 publications

A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase

A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase

Soluble MHC-Peptide Complexes Containing Long Rigid Linkers Abolish CTL-Mediated Cytotoxicity

The Trypanosoma brucei sphingolipid synthase, an essential enzyme and drug target

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