ArticleThe Journal of biological chemistry2015
Kinase activator-receiver preference in ErbB heterodimers is determined by intracellular regions and is not coupled to extracellular asymmetry.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Trans-activating mutations of the pseudokinase ERBB3.Oncogene · 2024Article
- TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression.Nature communications · 2023Article
- Potent molecular-targeted therapies for advanced esophageal squamous cell carcinoma.Therapeutic advances in medical oncology · 2023Review
- An Unbiased Functional Genetics Screen Identifies Rare Activating ERBB4 Mutations.Cancer research communications · 2022Article
- Glycosylation promotes the cancer regulator EGFR-ErbB2 heterodimer formation - molecular dynamics study.Journal of molecular modeling · 2021Article
- Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs.Biomolecules · 2021Review
- Kinetics of receptor tyrosine kinase activation define ERK signaling dynamics.Science signaling · 2020Article
- Mechanisms of Receptor Tyrosine-Protein Kinase ErbB-3 (ERBB3) Action in Human Neoplasia.The American journal of pathology · 2019Review
- Actionable Activating Oncogenic ERBB2/HER2 Transmembrane and Juxtamembrane Domain Mutations.Cancer cell · 2018Article
- Conformationally constrained peptides target the allosteric kinase dimer interface and inhibit EGFR activation.Bioorganic & medicinal chemistry · 2018Article
- Molecular dynamics simulations of asymmetric heterodimers of HER1/HER2 complexes.Journal of molecular modeling · 2017Article
- Piecing it together: Unraveling the elusive structure-function relationship in single-pass membrane receptors.Biochimica et biophysica acta. Biomembranes · 2017Review
- Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice.CNS neuroscience & therapeutics · 2017Article
- Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Effect of Spatial Inhomogeneities on the Membrane Surface on Receptor Dimerization and Signal Initiation.Frontiers in cell and developmental biology · 2016Article
- Analysis of the Role of the C-Terminal Tail in the Regulation of the Epidermal Growth Factor Receptor.Molecular and cellular biology · 2015Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The EGF receptor (EGFR) family comprises four homologs in humans collectively known as the ErbB or HER proteins. ErbB proteins are receptor tyrosine kinases that become activated when ligands bind to their extracellular regions and promote formation of specific homo- and heterodimers with enhanced tyrosine kinase activity. An essential feature of ErbB activation is formation of an asymmetric kinase dimer in which the C-terminal lobe of one kinase serves as the activator or donor kinase by binding the N-terminal lobe of a receiver or acceptor kinase and stabilizing its active conformation. ErbB extracellular regions are also thought to form active asymmetric dimers in which only one subunit binds ligand. The observation that the unliganded ErbB2 kinase preferentially serves as the activator kinase when paired with EGFR/ErbB1 implied that extracellular asymmetry in ErbB proteins might be coupled to intracellular asymmetry with unliganded partners favoring the activator kinase position. Using cell-based stimulation assays and chimeric ErbB proteins, we show that extracellular asymmetry is not coupled to intracellular asymmetry and that ErbB intracellular regions are sufficient to determine relative kinase activator-receiver orientation. We further show a hierarchy of activator-receiver preferences among ErbB proteins, with EGFR/ErbB1 being the strongest receiver, followed by ErbB2 and then ErbB4, and that cis-phosphorylation of EGFR and ErbB2 appears to be negligible. This hierarchy shapes the nature of signaling responses to different ligands in cells expressing multiple ErbB proteins.
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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.