ArticleThe Journal of general physiology2005
An electrostatic engine model for autoinhibition and activation of the epidermal growth factor receptor (EGFR/ErbB) family.
Article in The Journal of general physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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Who cites it
68 citing papers in PubMed, 138 citations in OpenAlex.
- Article
- Lipids regulate epidermal growth factor receptor activation by its ligands.Biochemical Society transactions · 2026Review
- Active regulation of the epidermal growth factor receptor by the membrane bilayer.bioRxiv : the preprint server for biology · 2025Article
- Structure and organization of full-length epidermal growth factor receptor in extracellular vesicles by cryo-electron tomography.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- 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
- Article
- Electric field modulation of ERK dynamics shows dependency on waveform and timing.Scientific reports · 2024Article
- Article
- Article
- Regulation of ErbB Receptors by the CaBiomedicines · 2023Review
- Ligand-induced transmembrane conformational coupling in monomeric EGFR.Nature communications · 2022Article
- CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma.Cancer cell international · 2021Article
- From Orai to E-Cadherin: Subversion of Calcium Trafficking in Cancer to Drive Proliferation, Anoikis-Resistance, and Metastasis.Biomedicines · 2020Review
- Receptor tyrosine kinase activation: From the ligand perspective.Current opinion in cell biology · 2020Review
- Coaction of Electrostatic and Hydrophobic Interactions: Dynamic Constraints on Disordered TrkA Juxtamembrane Domain.The journal of physical chemistry. B · 2019Article
- Controlling ERK Activation Dynamics in Mammary Epithelial Cells with Alternating Electric Fields through Microelectrodes.Nano letters · 2019Article
- Proteins with calmodulin-like domains: structures and functional roles.Cellular and molecular life sciences : CMLS · 2019Review
- The RTK Interactome: Overview and Perspective on RTK Heterointeractions.Chemical reviews · 2019Review
- The multifunctional role of phospho-calmodulin in pathophysiological processes.The Biochemical journal · 2018Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We propose a new mechanism to explain autoinhibition of the epidermal growth factor receptor (EGFR/ErbB) family of receptor tyrosine kinases based on a structural model that postulates both their juxtamembrane and protein tyrosine kinase domains bind electrostatically to acidic lipids in the plasma membrane, restricting access of the kinase domain to substrate tyrosines. Ligand-induced dimerization promotes partial trans autophosphorylation of ErbB1, leading to a rapid rise in intracellular [Ca(2+)] that can activate calmodulin. We postulate the Ca(2+)/calmodulin complex binds rapidly to residues 645--660 of the juxtamembrane domain, reversing its net charge from +8 to -8 and repelling it from the negatively charged inner leaflet of the membrane. The repulsion has two consequences: it releases electrostatically sequestered phosphatidylinositol 4,5-bisphosphate (PIP(2)), and it disengages the kinase domain from the membrane, allowing it to become fully active and phosphorylate an adjacent ErbB molecule or other substrate. We tested various aspects of the model by measuring ErbB juxtamembrane peptide binding to phospholipid vesicles using both a centrifugation assay and fluorescence correlation spectroscopy; analyzing the kinetics of interactions between ErbB peptides, membranes, and Ca(2+)/calmodulin using fluorescence stop flow; assessing ErbB1 activation in Cos1 cells; measuring fluorescence resonance energy transfer between ErbB peptides and PIP(2); and making theoretical electrostatic calculations on atomic models of membranes and ErbB juxtamembrane and kinase domains.
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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.