Evidence map›Paper›PMID 29326159›Full record

ArticleJournal of lipid research2018

An intrinsic lipid-binding interface controls sphingosine kinase 1 function.

Michael J Pulkoski-Gross, Meredith L Jenkins, Jean-Philip Truman, Mohamed F Salama, Christopher J Clarke, John E Burke, Yusuf A Hannun, Lina M Obeid

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 30 citations in OpenAlex.

  1. Structural dynamics of sphingosine kinase 1 regulation and inhibition.bioRxiv : the preprint server for biology · 2025
    Article
  2. Article
  3. Upregulation of sphingosine kinase 1 in response to doxorubicin generates an angiogenic response via stabilization of Snail.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Sphingosine kinase 1 downregulation is required for adaptation to serine deprivation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  9. Article
  10. Dissecting GCells · 2020
    Article
  11. Article
  12. Article
  13. Dynamic structural biology at the protein membrane interface.The Journal of biological chemistry · 2019
    Review
  14. Diacylglycerol kinases: Relationship to other lipid kinases.Advances in biological regulation · 2019
    Review
  15. Molecular mechanisms of regulation of sphingosine kinase 1.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018
    Review
  16. Sphingolipid biosynthesis in man and microbes.Natural product reports · 2018
    Review
  17. Article
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 3 countries.

Michael J Pulkoski-GrossDepartment of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11790.
Meredith L JenkinsDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8N 1A1, Canada.
Jean-Philip TrumanDepartment of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11790.
Mohamed F SalamaDepartment of Biochemistry, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35511, Egypt.
Christopher J ClarkeDepartment of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11790.
John E BurkeDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8N 1A1, Canada.
Yusuf A HannunDepartment of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11790.
Lina M ObeidDepartment of Medicine and Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11790 lina.obeid@stonybrookmedicine.edu.
Stony Brook University · USUniversity of Victoria · CAMansoura University · EGNorthport VA Medical Center · US

Funding

Sphingolipids in Cancer Therapy and AngiogenesisP01CA097132 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Daniel Canals · 2003 to 2026
$30.8M
Neutral Sphingomyelinases and Bioactive CeramidesR35GM118128 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2016 to 2025
$7.9M
CERAMIDE ACTIVATED PROTEIN PHOSPHATASESR01CA087584 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2000 to 2015
$4.2M
Role and Regulation of Ceramide Synthases in ApoptosisR01GM097741 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI LUBERTO, CHIARA · 2011 to 2019
$3.5M
Molecular Mechanisms of Regulation and Modulation of Sphingosine Kinase 1 Activity in CancerF31CA196315 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI PULKOSKI-GROSS, MICHAEL JOHN · 2016 to 2017
$66k
NCI NIH HHS F31 CA196315NCI NIH HHS P01 CA097132NCI NIH HHS R01 CA087584NIGMS NIH HHS R01 GM097741NIGMS NIH HHS R35 GM118128
6 · The paper itself

Abstract

Sphingosine kinase 1 (SK1) is required for production of sphingosine-1-phosphate (S1P) and thereby regulates many cellular processes, including cellular growth, immune cell trafficking, and inflammation. To produce S1P, SK1 must access sphingosine directly from membranes. However, the molecular mechanisms underlying SK1's direct membrane interactions remain unclear. We used hydrogen/deuterium exchange MS to study interactions of SK1 with membrane vesicles. Using the CRISPR/Cas9 technique to generate HCT116 cells lacking SK1, we explored the effects of membrane interface disruption and the function of the SK1 interaction site. Disrupting the interface resulted in reduced membrane association and decreased cellular SK1 activity. Moreover, SK1-dependent signaling, including cell invasion and endocytosis, was abolished upon mutation of the membrane-binding interface. Of note, we identified a positively charged motif on SK1 that is responsible for electrostatic interactions with membranes. Furthermore, we demonstrated that SK1 uses a single contiguous interface, consisting of an electrostatic site and a hydrophobic site, to interact with membrane-associated anionic phospholipids. Altogether, these results define a composite domain in SK1 that regulates its intrinsic ability to bind membranes and indicate that this binding is critical for proper SK1 function. This work will allow for a new line of thinking for targeting SK1 in disease.

Indexed as

Binding SitesCell MembraneDeuterium Exchange MeasurementHCT116 CellsHumansLipidsLysophospholipidsMass SpectrometryPhosphotransferases (Alcohol Group Acceptor)Signal TransductionSphingosineSphingosine KinaseLipidsLysophospholipidsPhosphotransferases (Alcohol Group Acceptor)Sphingosinesphingosine 1-phosphateSphingosine Kinasecell signalingenzyme regulationhydrogen-deuterium exchange mass spectrometrysphingolipidssphingosine-1-phosphate

Identifiers

PMID29326159
PMCPMC5832922
OpenAlexW2783960130

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.