Evidence map›Paper›PMID 30600259›Full record

ArticleScience signaling2019

Activation of atypical protein kinase C by sphingosine 1-phosphate revealed by an aPKC-specific activity reporter.

Taketoshi Kajimoto, Alisha D Caliman, Irene S Tobias, Taro Okada, Caila A Pilo, An-Angela N Van, J Andrew McCammon, Shun-Ichi Nakamura, Alexandra C Newton

Abstract read
In one paragraph

Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
–field-weighted citation impact
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

36 citing papers in PubMed.

  1. Review
  2. Article
  3. Protein Kinase C Regulates Meiosis in Mammalian Oocytes.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  4. Review
  5. Article
  6. Intracellular Sphingosine-1-Phosphate Induces Lipolysis Through Direct Activation of Protein Kinase C Zeta.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

9 authors.

Taketoshi KajimotoDepartment of Pharmacology, University of California at San Diego, La Jolla, CA 92037, USA. anewton@ucsd.edu tkajimot@med.kobe-u.ac.jp.ORCID 0000-0002-3855-1479
Alisha D CalimanDepartment of Pharmacology, University of California at San Diego, La Jolla, CA 92037, USA.ORCID 0000-0001-6344-1733
Irene S TobiasDepartment of Pharmacology, University of California at San Diego, La Jolla, CA 92037, USA.
Taro OkadaDivision of Biochemistry, Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.ORCID 0000-0001-5183-9402
Caila A PiloDepartment of Pharmacology, University of California at San Diego, La Jolla, CA 92037, USA.
An-Angela N VanDepartment of Pharmacology, University of California at San Diego, La Jolla, CA 92037, USA.
J Andrew McCammonDepartment of Pharmacology, University of California at San Diego, La Jolla, CA 92037, USA.ORCID 0000-0003-3065-1456
Shun-Ichi NakamuraDivision of Biochemistry, Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
Alexandra C NewtonDepartment of Pharmacology, University of California at San Diego, La Jolla, CA 92037, USA. anewton@ucsd.edu tkajimot@med.kobe-u.ac.jp.ORCID 0000-0002-2906-3705

Funding

Project# 4: INTERACTIONS OF ANCHORING PROTEINS WITH THEIR TARGETSP01DK054441 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TAYLOR, SUSAN S. · 1999 to 2017
$27.3M
National Biomedical Computation Resource - Competitive Revision SupplementP41GM103426 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AMARO, ROMMIE E · 2012 to 2019
$14.0M
GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
THEORY OF BIOMOLECULAR DIFFUSIONR01GM031749 · NIGMS · UNIVERSITY OF HOUSTON · PI HUBER, GARY ALEXANDER, MCCAMMON, JAMES ANDREW · 1985 to 2022
$7.8M
Molecular Mechanisms of Cell SignalingR35GM122523 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALEXANDRA C. NEWTON · 2017 to 2026
$6.7M
NIDDK NIH HHS P01 DK054441NIGMS NIH HHS P41 GM103426NIGMS NIH HHS R01 GM031749NIGMS NIH HHS R35 GM122523NIGMS NIH HHS T32 GM007752
6 · The paper itself

Abstract

Atypical protein kinase C (aPKC) isozymes are unique in the PKC superfamily in that they are not regulated by the lipid second messenger diacylglycerol, which has led to speculation about whether a different second messenger acutely controls their function. Here, using a genetically encoded reporter that we designed, aPKC-specific C kinase activity reporter (aCKAR), we found that the lipid mediator sphingosine 1-phosphate (S1P) promoted the cellular activity of aPKC. Intracellular S1P directly bound to the purified kinase domain of aPKC and relieved autoinhibitory constraints, thereby activating the kinase. In silico studies identified potential binding sites on the kinase domain, one of which was validated biochemically. In HeLa cells, S1P-dependent activation of aPKC suppressed apoptosis. Together, our findings identify a previously undescribed molecular mechanism of aPKC regulation, a molecular target for S1P in cell survival regulation, and a tool to further explore the biochemical and biological functions of aPKC.

Indexed as

Signal TransductionAnimalsApoptosisCell Line, TumorChlorocebus aethiopsCOS CellsEnzyme ActivationHeLa CellsHep G2 CellsHumansIsoenzymesLuminescent ProteinsLysophospholipidsMCF-7 CellsMicroscopy, FluorescenceMolecular Docking SimulationIsoenzymesLuminescent ProteinsLysophospholipidsPKC-3 proteinProtein Kinase CSphingosinesphingosine 1-phosphate

Identifiers

PMID30600259
PMCPMC6657501

What OpenQuestion holds

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Registered trials

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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.