ArticleMolecular cell2008
Comprehensive identification of PIP3-regulated PH domains from C. elegans to H. sapiens by model prediction and live imaging.
Article in Molecular cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 168 citations in OpenAlex.
- PI3K signaling in breast cancer: therapeutic advances versus adaptive resistance.The Journal of clinical investigation · 2026Review
- Review
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- Lysosomal PIPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Single-molecule lipid biosensors mitigate inhibition of endogenous effector proteins.The Journal of cell biology · 2025Article
- Single molecule Lipid Biosensors Mitigate Inhibition of Endogenous Effector Proteins.bioRxiv : the preprint server for biology · 2025Article
- Local administration of liposomal-based Plekhf1 gene therapy attenuates pulmonary fibrosis by modulating macrophage polarization.Science China. Life sciences · 2023Article
- Optogenetic dissection of RET signaling reveals robust activation of ERK and enhanced filopodia-like protrusions of regenerating axons.Molecular brain · 2023Article
- Structural Insights Uncover the Specific Phosphoinositide Recognition by the PH1 Domain of Arap3.International journal of molecular sciences · 2023Article
- Two cooperative binding sites sensitize PI(4,5)PScience advances · 2022Article
- Ceramide Kinase Inhibition Drives Ferroptosis and Sensitivity to Cisplatin in Mutant KRAS Lung Cancer by Dysregulating VDAC-Mediated Mitochondria Function.Molecular cancer research : MCR · 2022Article
- A CRISPR screen targeting PI3K effectors identifies RASA3 as a negative regulator of LFA-1-mediated adhesion in T cells.Science signaling · 2022Article
- The Amoebal Model for Macropinocytosis.Sub-cellular biochemistry · 2022Article
- Gradients of PI(4,5)PFrontiers in cell and developmental biology · 2022Article
- A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling.Nature communications · 2021Article
- Synthesis and Cellular Labeling of Multifunctional Phosphatidylinositol Bis- and Trisphosphate Derivatives.Angewandte Chemie (International ed. in English) · 2021Article
- Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins.Nature communications · 2021Article
- Leep1 interacts with PIP3 and the Scar/WAVE complex to regulate cell migration and macropinocytosis.The Journal of cell biology · 2021Article
- The present and future of PI3K inhibitors for cancer therapy.Nature cancer · 2021Article
- Signaling Heterogeneity is Defined by Pathway Architecture and Intercellular Variability in Protein Expression.iScience · 2021Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol(3,4,5)-trisphosphate (PIP3) control cell growth, migration, and other processes by recruiting proteins with pleckstrin homology (PH) domains and possibly other domains to the plasma membrane (PM). However, previous experimental and structural work with PH domains left conflicting evidence about which ones are PIP3 regulated. Here we used live-cell confocal imaging of 130 YFP-conjugated mouse PH domains and found that 20% translocated to the PM in response to receptor-generated PIP3 production. We developed a recursive-learning algorithm to predict PIP3 regulation of 1200 PH domains from different eukaryotes and validated that it accurately predicts PIP3 regulation. Strikingly, this algorithm showed that PIP3 regulation is specified by amino acids across the PH domain, not just the PIP3-binding pocket, and must have evolved several times independently from PIP3-insensitive ancestral PH domains. Finally, our algorithm and live-cell experiments provide a functional survey of PH domains in different species, showing that PI3K regulation increased from approximately two C. elegans and four Drosophila to 40 vertebrate proteins.
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Registered trials
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.