SPLASH (PLA2IID), a novel member of phospholipase A2 family, is associated with lymphotoxin deficiency

An, Shakhov; Rubtsov, AV; Lyakhov, IG; Tumanov, Alexei V.; Недоспасов, С А

doi:10.1038/sj.gene.6363659

Cited by 24 publications

(20 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accordance with a possible role as a Treg effector molecule, sPLA2-IID is predominantly expressed in spleen and lymph node (LN) with little or no expression in other tissues (16,18). We next investigated expression of sPLA2-IID in different cell types.…”

Section: Cd4mentioning

confidence: 99%

Secretory phospholipase A2-IID is an effector molecule of CD4⁺CD25⁺regulatory T cells

Allmen¹,

Schmitz²,

Bauer³

et al. 2009

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

View full text Add to dashboard Cite

Suppression by natural CD4 ؉ CD25 ؉ regulatory T cells (Tregs) is one mechanism by which tolerance is maintained. However, the way in which Tregs mediate suppression is not well understood. Here, we show that secreted phospholipase A2 (sPLA2)-IID is selectively produced by Tregs. sPLA2-IID is a potent mediator of Treg function, because it strongly suppressed proliferation of CD4 ؉ and CD8 ؉ T cells in vitro and in vivo in a manner independent of its catalytic activity. Furthermore, sPLA2-IID promoted the differentiation of Tregs, presumably via attenuating signaling through the PI3K/Akt/ mammalian target of rapamycin pathway. Importantly, administration of a sPLA2-IID-Fc fusion protein inhibited disease development in murine models of colitis and multiple sclerosis, suggesting that sPLA2-IID's immunosuppressive function might be exploited therapeutically.differential screening ͉ suppression ͉ tolerance

show abstract

Section: Cd4mentioning

confidence: 99%

Secretory phospholipase A2-IID is an effector molecule of CD4⁺CD25⁺regulatory T cells

Allmen¹,

Schmitz²,

Bauer³

et al. 2009

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

View full text Add to dashboard Cite

show abstract

“…The second transcript, which has a differently spliced first exon, and may have used an alternative transcription start, encodes the nonsecreted form of the enzyme (SPLASH). This form is associated with lymphotoxin deficiency (Shakhov et al 2000). Figure 6B shows four transcripts encoding seryl-tRNA synthase.…”

Section: Examplesmentioning

confidence: 99%

Splice Variation in Mouse Full-Length cDNAs Identified by Mapping to the Mouse Genome

Zavolan

Nimwegen²,

Gaasterland³

2002

Genome Res.

View full text Add to dashboard Cite

We mapped the collection of The Institute of Physical and Chemical Research (Japan) (RIKEN) 21,076 full-length mouse cDNA clone sequences and the mouse RefSeq sequences to the recently completed draft of the mouse genome. Using this mapping, we identified 3674 mouse genes with multiple transcripts, of which 1098 have splice variants. All but 532 of 21,076 clones (97.5%) mapped to the genome assembly. Alignments of cDNA clone sequences with proteins show that much of the detected splice variation alters coding regions and affects the translated protein. We developed novel analytical techniques to classify observed splice variation and to assess the relation between splice variation and alternative transcription. This analysis indicates that an alternative choice of transcription start or polyadenylation signal frequently induces splice variation.High-quality, full-length cDNA sequences mapped to a highquality complete genome assembly are crucial for the comprehensive analysis of splice variation. Analysis of 21,076 fulllength mouse cDNA clone sequences (RIKEN Genome Exploration Group Phase II Team and FANTOM Consortium. 2001) and of mouse RefSeq sequences (Pruitt and Maglott 2001) mapped to the complete mouse genome assembly (ftp:// ftp.ensembl.org/pub/assembly/mouse/mgsc_assembly_3) reveals numerous and complex patterns of splice variation. We developed stringent computational filters to identify and classify splice variants while eliminating cloning, sequencing, and mapping errors. Our computational pipeline identified 3674 mouse genes with multiple transcripts, 1098 of which (30%) have splice variants (Fig. 1). A total of 971 (88%) of the genes with alternative transcripts closely matched GenBank proteins (Benson et al. 2000). The protein-to-DNA alignments indicate that most of the splice variation affects transcriptcoding regions. The type of variation observed in initial and terminal exons indicates that alternative use of transcription start site and polyadenylation signals may be frequently responsible for the choice of splice signals flanking these exons.The variant transcripts reveal many known and novel forms of proteins, including variants of the myosin light chain, phospholipase A2, and a potassium ion channel with alternative 5Ј protein sequences, as well as a uridine diphosphate (UDP)-galactose transporter-related protein, variants of osmosis-responsive factor with different 5Ј untranslated region (UTR) sequences, and a new form of seryl-tRNA synthase with an internal in-frame extra coding exon. These examples illustrate the breadth of protein function affected by splice variation. They also illustrate a class of variation well represented in our data set, alternative exons possibly associated with alternative start of transcription.Prior large-scale studies of splice variation have used expressed sequence tag (EST) data to focus on two important (2000) used an alternative approach for identifying novel gene forms; they compiled a dataset of well-curated spliceosomal introns and identified alternat...

show abstract

“…24. Frozen 6-m sections were fixed in 4% paraformaldehyde/PBS solution for 10 min at room temperature, washed three times with PBS, and acetylated in 0.25% acetic anhydride for 10 min at room temperature.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Lymphotoxin and TNF Produced by B Cells Are Dispensable for Maintenance of the Follicle-Associated Epithelium but Are Required for Development of Lymphoid Follicles in the Peyer’s Patches

Tumanov

Kuprash

Mach

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Organogenesis of Peyer‘s patches (PP), follicle-associated epithelium, and M cells is impaired in mice lacking B cells. At the same time, lymphotoxin (LT) and TNF are known to be critical for the development of PP. To directly address the function of LT and TNF expressed by B cells in the maintenance of PP structure, we studied the de novo formation of PP in B cell-deficient mice after the transfer of bone marrow from mice with targeted mutations in LT, TNF, or their combinations. We found that although the compartmentalization of T and B cell zones and development of follicular dendritic cells were affected by the lack of B cell-derived LT and TNF, the development of follicle-associated epithelium and M cells in PP was completely independent of LT/TNF production by B cells.

show abstract

SPLASH (PLA2IID), a novel member of phospholipase A2 family, is associated with lymphotoxin deficiency

Cited by 24 publications

References 31 publications

Secretory phospholipase A2-IID is an effector molecule of CD4⁺CD25⁺regulatory T cells

Secretory phospholipase A2-IID is an effector molecule of CD4⁺CD25⁺regulatory T cells

Splice Variation in Mouse Full-Length cDNAs Identified by Mapping to the Mouse Genome

Lymphotoxin and TNF Produced by B Cells Are Dispensable for Maintenance of the Follicle-Associated Epithelium but Are Required for Development of Lymphoid Follicles in the Peyer’s Patches

Contact Info

Product

Resources

About

SPLASH (PLA2IID), a novel member of phospholipase A2 family, is associated with lymphotoxin deficiency

Cited by 24 publications

References 31 publications

Secretory phospholipase A2-IID is an effector molecule of CD4+CD25+regulatory T cells

Secretory phospholipase A2-IID is an effector molecule of CD4+CD25+regulatory T cells

Splice Variation in Mouse Full-Length cDNAs Identified by Mapping to the Mouse Genome

Lymphotoxin and TNF Produced by B Cells Are Dispensable for Maintenance of the Follicle-Associated Epithelium but Are Required for Development of Lymphoid Follicles in the Peyer’s Patches

Contact Info

Product

Resources

About

Secretory phospholipase A2-IID is an effector molecule of CD4⁺CD25⁺regulatory T cells

Secretory phospholipase A2-IID is an effector molecule of CD4⁺CD25⁺regulatory T cells