ArticleAdvances in biological regulation2013
Dynamic steps in receptor tyrosine kinase mediated activation of class IA phosphoinositide 3-kinases (PI3K) captured by H/D exchange (HDX-MS).
Article in Advances in biological regulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 96 citations in OpenAlex.
- Article
- Structures of the PI3Kα/KRas complex on lipid bilayers reveal molecular mechanisms of PI3Kα activation.Molecular cell · 2026Article
- Use of hydrogen deuterium exchange mass spectrometry in tandem with modern structural biology.The Biochemical journal · 2026Review
- A new functional assay reveals that membrane binding is critical for overactivation of the phosphoinositide 3-kinase H1047R mutant.The Journal of biological chemistry · 2026Article
- Family with sequence similarity 114 member A1 orchestrates immune evasion in triple-negative breast cancer.Signal transduction and targeted therapy · 2025Article
- Structural and allosteric effects of the membrane-bound PI3Kα H1047R mutation and opportunities for drug discovery.Communications chemistry · 2025Article
- Cancer-AssociatedInternational journal of medical sciences · 2025Review
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- 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
- Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain.bioRxiv : the preprint server for biology · 2023Article
- Oncogenic mutations of PIK3CA lead to increased membrane recruitment driven by reorientation of the ABD, p85 and C-terminus.Nature communications · 2023Article
- Cryo-EM structures of cancer-specific helical and kinase domain mutations of PI3Kα.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacy.Cancer discovery · 2022Article
- The orchestrated signaling by PI3Kα and PTEN at the membrane interface.Computational and structural biotechnology journal · 2022Review
- Single-molecule studies reveal regulatory interactions between master kinases PDK1, AKT1, and PKC.Biophysical journal · 2021Article
- Cryo-EM structures of PI3Kα reveal conformational changes during inhibition and activation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- PI3Kδ Forms Distinct Multiprotein Complexes at the TCR Signalosome in Naïve and Differentiated CD4Frontiers in immunology · 2021Article
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2 authors at 2 institutions in 1 country.
Funding
Abstract
The catalytic subunits of all class IA phosphoinositide 3-kinases (PI3Ks) associate with identical p85-related subunits and phosphorylate PIP2 yielding PIP3, but they can vary greatly in the signaling pathways in which they participate. The binding of the p85 subunit to the p110 catalytic subunits is constitutive, and this inhibits activity, but some of the inhibitory contacts are reversible and subject to regulation. Interaction with phosphotyrosine-containing peptides (RTK-pY) releases a subset of these inhibitory contacts. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) provides a map of the dynamic interactions unique to each of the isotypes. RTK-pY binding exposes the p110 helical domains for all class IA enzymes (due to release of the nSH2 contact) and exposes the C-lobe of the kinase domains of p110β and p110δ (resulting from release of the cSH2 contact). Consistent with this, our in vitro assays show that all class IA isoforms are inhibited by the nSH2, but only p110β and p110δ are inhibited by the cSH2. While a C2/iSH2 inhibitory contact exists in all isoforms, HDX indicates that p110β releases this contact most readily. The unique dynamic relationships of the different p110 isozymes to the p85 subunit may facilitate new strategies for specific inhibitors of the PI3Ks.
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