Evidence map›Paper›PMID 25002116›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014

Role of sphingosine kinase 1 and sphingosine-1-phosphate in CD40 signaling and IgE class switching.

Eugene Y Kim, Jamie L Sturgill, Nitai C Hait, Dorit Avni, Evelyn C Valencia, Michael Maceyka, Santiago Lima, Jeremy Allegood, Wei-Ching Huang, Shijun Zhang and 3 more

Open access · greenAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 37% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Loss of sphingosine kinase 2 protects against cisplatin-induced kidney injury.American journal of physiology. Renal physiology · 2022
    Article
  3. Sphingolipids and their enigmatic role in asthma.Advances in biological regulation · 2018
    Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Eugene Y KimDepartment of Biochemistry and Molecular Biology.
Jamie L SturgillDepartment of Microbiology and Immunology, and.
Nitai C HaitDepartment of Biochemistry and Molecular Biology.
Dorit AvniDepartment of Biochemistry and Molecular Biology.
Evelyn C ValenciaDepartment of Biochemistry and Molecular Biology.
Michael MaceykaDepartment of Biochemistry and Molecular Biology.
Santiago LimaDepartment of Biochemistry and Molecular Biology.
Jeremy AllegoodDepartment of Biochemistry and Molecular Biology.
Wei-Ching HuangDepartment of Biochemistry and Molecular Biology.
Shijun ZhangDepartment of Medicinal Chemistry, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
Sheldon MilstienDepartment of Biochemistry and Molecular Biology.
Daniel ConradDepartment of Microbiology and Immunology, and.
Sarah SpiegelDepartment of Biochemistry and Molecular Biology, sspiegel@vcu.edu.
Virginia Commonwealth University · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Keri R Maher · 1985 to 2026
$51.0M
The Effect of Lyn Deficiency on Mast Cell Activation and Inflammatory Disease ProU19AI077435 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI SCHWARTZ, LAWRENCE B. · 2008 to 2012
$7.7M
Virginia Commonwealth University Initiative for Maximizing Student DevelopmentR25GM090084 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI AKBARALI, HAMID I, LLOYD, JOYCE A. · 2010 to 2022
$5.2M
VCU Neuroscience Center Core GrantP30NS047463 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI POVLISHOCK, JOHN T · 2003 to 2013
$5.0M
SPHINGOSINE AS A MODULATOR OF CELLULAR PROLIFERATIONR01GM043880 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 1990 to 2023
$3.8M
Sphingosine Kinases in Cancer Cell SignalingR01CA061774 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 1994 to 2015
$3.8M
Sphingosine-1 phosphate phosphohydrolaseR37GM043880 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 2003 to 2012
$3.2M
Targeting sphingosine kinases in FceRI-mediated allergic responsesR01AI050094 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 2002 to 2012
$2.9M
Training In Functional Lipidomics In Cardiovascular & Respiratory DiseasesT32HL094290 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SPIEGEL, SARAH · 2009 to 2013
$1.2M
NCI NIH HHS P30 CA016059NCI NIH HHS P30CA16059NCI NIH HHS R01 CA061774NHLBI NIH HHS T32 HL094290NHLBI NIH HHS T32HL094290NIAID NIH HHS R01 AI050094NIAID NIH HHS R01AI50094NIAID NIH HHS U19 AI077435NIAID NIH HHS U19AI077435NIGMS NIH HHS R01 GM043880NIGMS NIH HHS R25 GM090084NIGMS NIH HHS R37 GM043880NIGMS NIH HHS R37GM043880NINDS NIH HHS P30 NS047463NINDS NIH HHS P30NS047463
6 · The paper itself

Abstract

The tumor necrosis factor (TNF) receptor family member CD40 plays an essential role in the activation of antigen-presenting cells, B cell maturation, and immunoglobulin (Ig) class switching critical for adaptive immunity. Although the bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) and the kinase that produces it, sphingosine kinase 1 (SphK1), have long been implicated in the actions of TNF mediated by engagement of TNFR1, nothing is yet known of their role in CD40-mediated events. We have now found that ligation of CD40 activates and translocates SphK1 to the plasma membrane, leading to generation of S1P. SphK1 inhibition in human tonsil B cells, as well as inhibition or deletion of SphK1 in mouse splenic B cells, significantly reduced CD40-mediated Ig class switching and plasma cell differentiation ex vivo. Optimal activation of downstream CD40 signaling pathways, including NF-κB, p38, and JNK, also required SphK1. In mice treated with a SphK1 inhibitor or in SphK1(-/-) mice, isotype switching to antigen-specific IgE was decreased in vivo by 70 and 55%, respectively. Our results indicate that SphK1 is important for CD40-mediated B cell activation and regulation of humoral responses and suggest that targeting SphK1 might be a useful therapeutic approach to control antigen-specific IgE production.

Indexed as

Immunoglobulin Class SwitchingAnimalsB-LymphocytesCD40 AntigensCell DifferentiationCell MembraneHEK293 CellsHumansImmunoglobulin ELysophospholipidsMAP Kinase Kinase 4MiceMice, Inbred C57BLNF-kappa Bp38 Mitogen-Activated Protein KinasesPhosphotransferases (Alcohol Group Acceptor)CD40 AntigensImmunoglobulin ELysophospholipidsMAP Kinase Kinase 4NF-kappa Bp38 Mitogen-Activated Protein KinasesPhosphotransferases (Alcohol Group Acceptor)Sphingosinesphingosine 1-phosphateSphingosine KinaseB cellsinflammationNF-κBsphingolipids

Identifiers

PMID25002116
PMCPMC4202100
OpenAlexW2029757123

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.