Evidence map›Paper›PMID 30442661›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Quantitation of class IA PI3Ks in mice reveals p110-free-p85s and isoform-selective subunit associations and recruitment to receptors.

N Tsolakos, T N Durrant, T Chessa, S M Suire, D Oxley, S Kulkarni, J Downward, O Perisic, R L Williams, L Stephens and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

35 citing papers in PubMed, 54 citations in OpenAlex.

  1. PI(3,5)PScience advances · 2026
    Article
  2. A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026
    Review
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  16. Review
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  19. Article
  20. Phosphoinositide 3-Kinases as Potential Targets for Thrombosis Prevention.International journal of molecular sciences · 2022
    Review
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

11 authors at 4 institutions in 1 country.

N TsolakosThe Signaling Department, The Babraham Institute, CB22 3AT Cambridge, United Kingdom.
T N DurrantDepartment of Chemistry, University of Oxford, OX1 3QZ Oxford, United Kingdom.
T ChessaThe Signaling Department, The Babraham Institute, CB22 3AT Cambridge, United Kingdom.
S M SuireThe Signaling Department, The Babraham Institute, CB22 3AT Cambridge, United Kingdom.
D OxleyThe Mass Spec Facility, The Babraham Institute, CB22 3AT Cambridge, United Kingdom.
S KulkarniThe Signaling Department, The Babraham Institute, CB22 3AT Cambridge, United Kingdom.
J DownwardThe Oncogene Biology Lab, The Francis Crick Institute, NW1 1AT London, United Kingdom.
O PerisicProtein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, CB2 0QH Cambridge, United Kingdom.
R L WilliamsProtein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, CB2 0QH Cambridge, United Kingdom.ORCID 0000-0001-7754-4207
L StephensThe Signaling Department, The Babraham Institute, CB22 3AT Cambridge, United Kingdom; len.stephens@babraham.ac.uk phillip.hawkins@babraham.ac.uk.
P T HawkinsThe Signaling Department, The Babraham Institute, CB22 3AT Cambridge, United Kingdom; len.stephens@babraham.ac.uk phillip.hawkins@babraham.ac.uk.
Babraham Institute · GBMRC Laboratory of Molecular Biology · GBThe Francis Crick Institute · GBUniversity of Oxford · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J004456/1Biotechnology and Biological Sciences Research Council BBS/E/B/0000H235Biotechnology and Biological Sciences Research Council BBS/E/B/000C0413Medical Research Council MC_U105184308Medical Research Council MR/R000409/1Wellcome TrustWellcome Trust WT085889MA
6 · The paper itself

Abstract

Class IA PI3Ks have many roles in health and disease. The rules that govern intersubunit and receptor associations, however, remain unclear. We engineered mouse lines in which individual endogenous class IA PI3K subunits were C-terminally tagged with 17aa that could be biotinylated in vivo. Using these tools we quantified PI3K subunits in streptavidin or PDGFR pull-downs and cell lysates. This revealed that p85α and β bound equivalently to p110α or p110β but p85α bound preferentially to p110δ. p85s were found in molar-excess over p110s in a number of contexts including MEFs (p85β, 20%) and liver (p85α, 30%). In serum-starved MEFs, p110-free-p85s were preferentially, compared with heterodimeric p85s, bound to PDGFRs, consistent with in vitro assays that demonstrated they bound PDGFR-based tyrosine-phosphorylated peptides with higher affinity and co-operativity; suggesting they may act to tune a PI3K activation threshold. p110α-heterodimers were recruited 5-6× more efficiently than p110β-heterodimers to activated PDGFRs in MEFs or to PDGFR-based tyrosine-phosphorylated peptides in MEF-lysates. This suggests that PI3Kα has a higher affinity for relevant tyrosine-phosphorylated motifs than PI3Kβ. Nevertheless, PI3Kβ contributes substantially to acute PDGF-stimulation of PIP

Indexed as

AnimalsClass Ia Phosphatidylinositol 3-KinaseDimerizationFibroblastsMiceMice, Inbred C57BLPhosphorylationProtein BindingProtein IsoformsReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorSignal TransductionClass Ia Phosphatidylinositol 3-KinaseProtein IsoformsReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorAvi-tagisoform-selectivePI3K

Identifiers

PMID30442661
PMCPMC6275495
OpenAlexW2900905486

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.