ArticleProceedings of the National Academy of Sciences of the United States of America2021
Scaffolding mechanism of arrestin-2 in the cRaf/MEK1/ERK signaling cascade.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. 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, 49 citations in OpenAlex.
- Targeting tumor-associated G-protein coupled receptors: beyond single-axis inhibition toward multidimensional regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Phosphoregulation of the novel hemi-arrestin MAPK scaffold Sms1 prevents untimely mating.Nature communications · 2026Article
- Arrestin-3 sca-olds multiple MAP3Ks driving stress-induced JNK3 activation and cell death.bioRxiv : the preprint server for biology · 2026Article
- Functional and structural insights into interactions between β-Arrestin 1 and Gαs or Gαi1.Nature communications · 2026Article
- Arrestins as Possible Drug Targets.Biomolecules & therapeutics · 2025Review
- Astrocyte FGF7/FGFR2 autocrine signaling mediates neuroinflammation and promotes MPTP-induced degeneration of dopaminergic neurons.Acta pharmaceutica Sinica. B · 2025Article
- Molecular mechanism of β-arrestin 2 interaction with phosphorylated intracellular loop 3 of dopamine receptor D2.Communications biology · 2025Article
- Molecular mechanism of β-arrestin-2 pre-activation by phosphatidylinositol 4,5-bisphosphate.EMBO reports · 2024Article
- Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells.Biomolecules & therapeutics · 2024Article
- Emerging mechanistic understanding of cilia function in cellular signalling.Nature reviews. Molecular cell biology · 2024Review
- The CNK-HYP scaffolding complex promotes RAF activation by enhancing KSR-MEK interaction.Nature structural & molecular biology · 2024Article
- GPCR-dependent and -independent arrestin signaling.Trends in pharmacological sciences · 2024Review
- Loss of β-arrestin2 aggravated condylar cartilage degeneration at the early stage of temporomandibular joint osteoarthritis.BMC musculoskeletal disorders · 2024Article
- Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq.Communications biology · 2024Article
- PRL-mediated STAT5B/ARRB2 pathway promotes the progression of prostate cancer through the activation of MAPK signaling.Cell death & disease · 2024Article
- β-adrenergic receptor signaling mediated by β-arrestins and its potential role in heart failure.Current opinion in physiology · 2024Article
- Adaptor molecules mediate negative regulation of macrophage inflammatory pathways: a closer look.Frontiers in immunology · 2024Review
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- Distinct activation mechanisms of β-arrestin-1 revealed byNature communications · 2023Article
- Fluorescent biosensors illuminate the spatial regulation of cell signaling across scales.The Biochemical journal · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Arrestins were initially identified for their role in homologous desensitization and internalization of G protein-coupled receptors. Receptor-bound arrestins also initiate signaling by interacting with other signaling proteins. Arrestins scaffold MAPK signaling cascades, MAPK kinase kinase (MAP3K), MAPK kinase (MAP2K), and MAPK. In particular, arrestins facilitate ERK1/2 activation by scaffolding ERK1/2 (MAPK), MEK1 (MAP2K), and Raf (MAPK3). However, the structural mechanism underlying this scaffolding remains unknown. Here, we investigated the mechanism of arrestin-2 scaffolding of cRaf, MEK1, and ERK2 using hydrogen/deuterium exchange-mass spectrometry, tryptophan-induced bimane fluorescence quenching, and NMR. We found that basal and active arrestin-2 interacted with cRaf, while only active arrestin-2 interacted with MEK1 and ERK2. The ATP binding status of MEK1 or ERK2 affected arrestin-2 binding; ATP-bound MEK1 interacted with arrestin-2, whereas only empty ERK2 bound arrestin-2. Analysis of the binding interfaces suggested that the relative positions of cRaf, MEK1, and ERK2 on arrestin-2 likely facilitate sequential phosphorylation in the signal transduction cascade.
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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.