Evidence map›Paper›PMID 42349404›Full record

ArticleMolecular cell2026

Structures of the PI3Kα/KRas complex on lipid bilayers reveal molecular mechanisms of PI3Kα activation.

Hayarpi Torosyan, Michael D Paul, Brigitte G Meyer, Allison Maker, Natalia Jura, Kliment A Verba

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Hayarpi TorosyanCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Michael D PaulCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Brigitte G MeyerCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Allison MakerCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Natalia JuraCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: natalia.jura@ucsf.edu.
Kliment A VerbaDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: kliment.verba@ucsf.edu.

Funding

The Cancer Cell Map Initiative v2.0U54CA274502 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trey Ideker, Nevan J Krogan · 2022 to 2026
$14.2M
Structural and Functional Studies of HER ReceptorsR35GM139636 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Natalia Jura · 2021 to 2026
$2.5M
Molecular mechanisms of Ras and Receptor Tyrosine Kinase Convergence on PI3K in cancerR37CA308018 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kliment A Verba · 2026 to 2026
$636k
NCI NIH HHS R37 CA308018NCI NIH HHS U54 CA274502NIGMS NIH HHS R35 GM139636
6 · The paper itself

Abstract

PI3Kα is a potent oncogene that converts PIP2 to PIP3 at the plasma membrane upon activation by receptor tyrosine kinases and Ras. To understand the molecular mechanism of PI3Kα activation, we used cryo-electron microscopy to visualize the conformational states that underlie its transition to an active signaling complex. Here, we present structures of the PI3Kα/KRas complex embedded in lipid nanodiscs, revealing a rich ensemble of PI3Kα conformations that capture the progressive release of key inhibitory domains from the PI3Kα catalytic core. PIP2 triggers significant restructuring of active site regulatory motifs while an activating phosphopeptide induces dimerization of the PI3Kα/KRas complex through a p110α catalytic subunit-mediated interface that is sterically occluded in autoinhibited PI3Kα. In cells, dimeric PI3Kα amplifies Akt signaling in response to growth factor stimulation. Collectively, these structures map the conformational landscape of PI3Kα activation and reveal previously unexplored interfaces for potential therapeutic targeting.

Indexed as

Lipid BilayersProto-Oncogene Proteins p21(ras)AnimalsCatalytic DomainCryoelectron MicroscopyEnzyme ActivationHumansModels, MolecularPhosphatidylinositol 3-KinasesProtein BindingProtein ConformationProtein MultimerizationProto-Oncogene Proteins c-aktSignal TransductionKRAS protein, humanLipid BilayersPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)cryo-EMnanodiscp110p85phosphotyrosinePI3KPIP2Rassignalingsignalosome

Identifiers

PMID42349404
PMCPMC13403991

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.