ArticleBiochemistry2011
Nonvisual arrestins function as simple scaffolds assembling the MKK4-JNK3α2 signaling complex.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
41 citing papers in PubMed, 64 citations in OpenAlex.
- Arrestin-3 sca-olds multiple MAP3Ks driving stress-induced JNK3 activation and cell death.bioRxiv : the preprint server for biology · 2026Article
- Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral sensitization.Cell reports. Medicine · 2024Article
- GPCR-dependent and -independent arrestin signaling.Trends in pharmacological sciences · 2024Review
- Arrestins: A Small Family of Multi-Functional Proteins.International journal of molecular sciences · 2024Review
- Expression of Untagged Arrestins in E. coli and Their Purification.Current protocols · 2023Article
- Arrestin-3-Dependent Activation of c-Jun N-Terminal Kinases (JNKs).Current protocols · 2023Article
- Review
- Short Arrestin-3-Derived Peptides Activate JNK3 in Cells.International journal of molecular sciences · 2022Article
- Colocalization and Interaction Study of Neuronal JNK3, JIP1, and β-Arrestin2 Together with PSD95.International journal of molecular sciences · 2022Article
- Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins.International journal of molecular sciences · 2022Review
- Scaffolding mechanism of arrestin-2 in the cRaf/MEK1/ERK signaling cascade.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Biased GPCR signaling: Possible mechanisms and inherent limitations.Pharmacology & therapeutics · 2020Review
- Targeting arrestin interactions with its partners for therapeutic purposes.Advances in protein chemistry and structural biology · 2020Review
- Arrestin-3 interaction with maternal embryonic leucine-zipper kinase.Cellular signalling · 2019Article
- Plethora of functions packed into 45 kDa arrestins: biological implications and possible therapeutic strategies.Cellular and molecular life sciences : CMLS · 2019Review
- The structural basis of the arrestin binding to GPCRs.Molecular and cellular endocrinology · 2019Review
- Cleavage of arrestin-3 by caspases attenuates cell death by precluding arrestin-dependent JNK activation.Cellular signalling · 2019Article
- GPCR Signaling Regulation: The Role of GRKs and Arrestins.Frontiers in pharmacology · 2019Review
- Using In Vitro Pull-Down and In-Cell Overexpression Assays to Study Protein Interactions with Arrestin.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Arrestin-mediated signaling: Is there a controversy?World journal of biological chemistry · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Arrestins make up a small family of proteins with four mammalian members that play key roles in the regulation of multiple G protein-coupled receptor-dependent and -independent signaling pathways. Although arrestins were reported to serve as scaffolds for MAP kinase cascades, promoting the activation of JNK3, ERK1/2, and p38, the molecular mechanisms involved were not elucidated, and even the direct binding of arrestins with MAP kinases was never demonstrated. Here, using purified proteins, we show that both nonvisual arrestins directly bind JNK3α2 and its upstream activator MKK4, and that the affinity of arrestin-3 for these kinases is higher than that of arrestin-2. Reconstitution of the MKK4-JNK3α2 signaling module from pure proteins in the presence of different arrestin-3 concentrations showed that arrestin-3 acts as a "true" scaffold, facilitating JNK3α2 phosphorylation by bringing the two kinases together. Both the level of JNK3α2 phosphorylation by MKK4 and JNK3α2 activity toward its substrate ATF2 increase at low and then decrease at high arrestin-3 levels, yielding a bell-shaped concentration dependence expected with true scaffolds that do not activate the upstream kinase or its substrate. Thus, direct binding of both kinases and true scaffolding is the molecular mechanism of action of arrestin-3 on the MKK4-JNK3α2 signaling module.
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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.