ArticlePflugers Archiv : European journal of physiology2011
Phosphatidylinositol-4,5-bisphosphate regulates epidermal growth factor receptor activation.
Article in Pflugers Archiv : European journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 108 citations in OpenAlex.
- Integrative structural and dynamics studies of epidermal growth factor receptor (EGFR).Experimental & molecular medicine · 2026Review
- Article
- Lipids regulate epidermal growth factor receptor activation by its ligands.Biochemical Society transactions · 2026Review
- EGFR activation requires cholesterol interaction at the inner leaflet of the plasma membrane.Science advances · 2025Article
- Active regulation of the epidermal growth factor receptor by the membrane bilayer.bioRxiv : the preprint server for biology · 2025Article
- Review
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- The Influence of Phosphoinositide Lipids in the Molecular Biology of Membrane Proteins: Recent Insights from Simulations.Journal of molecular biology · 2025Review
- Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes.Science advances · 2024Article
- How Neuromembrane Lipids Modulate Membrane Proteins: Insights from G-Protein-Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs).Cold Spring Harbor perspectives in biology · 2023Review
- The Activation Mechanism of the Insulin Receptor: A Structural Perspective.Annual review of biochemistry · 2023Review
- Molecular Biophysics of Class A G Protein Coupled Receptors-Lipids Interactome at a Glance-Highlights from the ABiomolecules · 2023Review
- Endocytosis at the Crossroad of Polarity and Signaling Regulation: Learning fromInternational journal of molecular sciences · 2022Review
- Review
- βA3/A1-crystallin regulates apical polarity and EGFR endocytosis in retinal pigmented epithelial cells.Communications biology · 2021Article
- Multi-scale simulations of the T cell receptor reveal its lipid interactions, dynamics and the arrangement of its cytoplasmic region.PLoS computational biology · 2021Article
- Lattice complex assembled by noncompetitive anti-EGFR antibodies regulates actin cytoskeletal reorganization.Cancer cell international · 2020Article
- Coaction of Electrostatic and Hydrophobic Interactions: Dynamic Constraints on Disordered TrkA Juxtamembrane Domain.The journal of physical chemistry. B · 2019Article
- EGFR/ErbB Inhibition Promotes OPC Maturation up to Axon Engagement by Co-Regulating PIP2 and MBP.Cells · 2019Article
- Membrane Recognition and Binding by the Phosphatidylinositol Phosphate Kinase PIP5K1A: A Multiscale Simulation Study.Structure (London, England : 1993) · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P(2) or PIP(2)] is a direct modulator of a diverse array of proteins in eukaryotic cells. The functional integrity of transmembrane proteins, such as ion channels and transporters, is critically dependent on specific interactions with PIP(2) and other phosphoinositides. Here, we report a novel requirement for PIP(2) in the activation of the epidermal growth factor receptor (EGFR). Down-regulation of PIP(2) levels either via pharmacological inhibition of PI kinase activity, or via manipulation of the levels of the lipid kinase PIP5K1α and the lipid phosphatase synaptojanin, reduced EGFR tyrosine phosphorylation, whereas up-regulation of PIP(2) levels via overexpression of PIP5K1α had the opposite effect. A cluster of positively charged residues in the juxtamembrane domain (basic JD) of EGFR is likely to mediate binding of EGFR to PIP(2) and PIP(2)-dependent regulation of EGFR activation. A peptide mimicking the EGFR juxtamembrane domain that was assayed by surface plasmon resonance displayed strong binding to PIP(2). Neutralization of positively charged amino acids abolished EGFR/PIP(2) interaction in the context of this peptide and down-regulated epidermal growth factor (EGF)-induced EGFR auto-phosphorylation and EGF-induced EGFR signaling to ion channels in the context of the full-length receptor. These results suggest that EGFR activation and downstream signaling depend on interactions of EGFR with PIP(2) and point to the basic JD's critical involvement in these interactions. The addition of this very different class of membrane proteins to ion channels and transporters suggests that PIP(2) may serve as a general modulator of the activity of many diverse eukaryotic transmembrane proteins through their basic JDs.
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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 OpenQuestion graph.