ArticleThe Journal of biological chemistry2017
Kinetic and structural analyses reveal residues in phosphoinositide 3-kinase α that are critical for catalysis and substrate recognition.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Molecular architecture responsible for specific inhibition of oncogenic PI3KActa pharmaceutica Sinica. B · 2026Article
- Understanding the conformational dynamics of PI3Kα due to helical domain mutations: insights from Markov state model analysis.Molecular diversity · 2025Article
- Structural and allosteric effects of the membrane-bound PI3Kα H1047R mutation and opportunities for drug discovery.Communications chemistry · 2025Article
- Mechanism of Myh3 gene regulation of intramuscular fat content in Beijing black pigs via the MAPK signaling pathway.BMC genomics · 2025Article
- Improved production of class I phosphatidylinositol 4,5-bisphosphate 3-kinase.Protein expression and purification · 2025Article
- Molecular Basis of Oncogenic PI3K Proteins.Cancers · 2024Review
- ATP-competitive inhibitors of PI3K enzymes demonstrate an isoform selective dual action by controlling membrane binding.The Biochemical journal · 2024Article
- PI3K-AKT-mediated phosphorylation of Thr260 in CgCaspase-3/6/7 regulates heat-induced activation in oysters.Communications biology · 2024Article
- Identification of Novel PI3Kα Inhibitor Against Gastric Cancer: QSAR-, Molecular Docking-, and Molecular Dynamics Simulation-Based Analysis.Applied biochemistry and biotechnology · 2024Article
- Identification of immunostimulatory activities and active compounds from sequentially extracted fractions of rhizosphere fungal fermentation broth ofFrontiers in pharmacology · 2024Article
- Inhibition of phosphatidylinositol 3-kinase catalytic subunit alpha by miR-203a-3p reduces hypertrophic scar formation via phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway.Burns & trauma · 2024Article
- Structural and mechanistic insights provided by single particle cryo-EM analysis of phosphoinositide 3-kinase (PI3Kα).Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Article
- At a crossroads: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy.Nature reviews. Clinical oncology · 2022Review
- Recent Advances in the Biological Activity of s-Triazine Core Compounds.Pharmaceuticals (Basel, Switzerland) · 2022Review
- The orchestrated signaling by PI3Kα and PTEN at the membrane interface.Computational and structural biotechnology journal · 2022Review
- Modeling Kaempferol as a Potential Pharmacological Agent for COVID-19/PF Co-Occurrence Based on Bioinformatics and System Pharmacological Tools.Frontiers in pharmacology · 2022Article
- Class I PI3K Biology.Current topics in microbiology and immunology · 2022Article
- Therapeutic implications of activating noncanonical PIK3CA mutations in head and neck squamous cell carcinoma.The Journal of clinical investigation · 2021Article
- How Far Are We from the Rapid Prediction of Drug Resistance Arising Due to Kinase Mutations?ACS omega · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Phosphoinositide 3-kinases (PI3Ks) are ubiquitous lipid kinases that activate signaling cascades controlling cell survival, proliferation, protein synthesis, and vesicle trafficking. PI3Ks have dual kinase specificity: a lipid kinase activity that phosphorylates the 3'-hydroxyl of phosphoinositides and a protein-kinase activity that includes autophosphorylation. Despite the wealth of biochemical and structural information on PI3Kα, little is known about the identity and roles of individual active-site residues in catalysis. To close this gap, we explored the roles of residues of the catalytic domain and the regulatory subunit of human PI3Kα in lipid and protein phosphorylation. Using site-directed mutagenesis, kinetic assays, and quantitative mass spectrometry, we precisely mapped key residues involved in substrate recognition and catalysis by PI3Kα. Our results revealed that Lys-776, located in the P-loop of PI3Kα, is essential for the recognition of lipid and ATP substrates and also plays an important role in PI3Kα autophosphorylation. Replacement of the residues His-936 and His-917 in the activation and catalytic loops, respectively, with alanine dramatically changed PI3Kα kinetics. Although H936A inactivated the lipid kinase activity without affecting autophosphorylation, H917A abolished both the lipid and protein kinase activities of PI3Kα. On the basis of these kinetic and structural analyses, we propose possible mechanistic roles of these critical residues in PI3Kα catalysis.
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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 Socratic graph.