ArticleFrontiers in neuroscience2020
Binding of the Human 14-3-3 Isoforms to Distinct Sites in the Leucine-Rich Repeat Kinase 2.
Article in Frontiers in neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- Chemical Genetic Targeting of the LRRK2 GTPase Domain.bioRxiv : the preprint server for biology · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- The structural basis for LRRK2's activation and autoinhibition.bioRxiv : the preprint server for biology · 2026Article
- 14-3-3 binding maintains the Parkinson's associated kinase LRRK2 in an inactive state.Nature communications · 2025Article
- Article
- Electroacupuncture alleviates Parkinson's disease by targeting HDAC/SIRT-mediated deacetylation of 14-3-3.Frontiers in aging neuroscience · 2025Article
- 14-3-3 phosphorylation inhibits 14-3-3θ's ability to regulate LRRK2 kinase activity and toxicity.Human molecular genetics · 2024Article
- Development of a NanoBRET assay for evaluation of 14-3-3σ molecular glues.SLAS discovery : advancing life sciences R & D · 2024Article
- Toxic interactions between dopamine, α-synuclein, monoamine oxidase, and genes in mitochondria of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- RedOx regulation of LRRK2 kinase activity by active site cysteines.NPJ Parkinson's disease · 2024Article
- Role of the leucine-rich repeat protein kinase 2 C-terminal tail in domain cross-talk.The Biochemical journal · 2024Article
- Prospective Role of PAK6 and 14-3-3γ as Biomarkers for Parkinson's Disease.Journal of Parkinson's disease · 2024Article
- A leucine-rich repeat kinase 2 (LRRK2) pathway biomarker characterization study in patients with Parkinson's disease with and without LRRK2 mutations and healthy controls.Clinical and translational science · 2023Article
- Structural mapping of PEAK pseudokinase interactions identifies 14-3-3 as a molecular switch for PEAK3 signaling.Nature communications · 2023Article
- Capturing Differences in the Regulation of LRRK2 Dynamics and Conformational States by Small Molecule Kinase Inhibitors.ACS chemical biology · 2023Article
- LRRK2 Structure-Based Activation Mechanism and Pathogenesis.Biomolecules · 2023Review
- MIND-S is a deep-learning prediction model for elucidating protein post-translational modifications in human diseases.Cell reports methods · 2023Article
- 14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson's disease-like motor incoordination in mice.Molecular brain · 2023Article
- PAK6-mediated phosphorylation of PPP2R2C regulates LRRK2-PP2A complex formation.Frontiers in molecular neuroscience · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteins of the 14-3-3 family are well known modulators of the leucine-rich repeat kinase 2 (LRRK2) regulating kinase activity, cellular localization, and ubiquitylation. Although binding between those proteins has been investigated, a comparative study of all human 14-3-3 isoforms interacting with LRRK2 is lacking so far. In a comprehensive approach, we quantitatively analyzed the interaction between the seven human 14-3-3 isoforms and LRRK2-derived peptides covering both, reported and putative 14-3-3 binding sites. We observed that phosphorylation is an absolute prerequisite for 14-3-3 binding and generated binding patterns of 14-3-3 isoforms to interact with peptides derived from the N-terminal phosphorylation cluster (S910 and S935), the Roc domain (S1444) and the C-terminus. The tested 14-3-3 binding sites in LRRK2 preferentially were recognized by the isoforms γ and η, whereas the isoforms ϵ and especially σ showed the weakest or no binding. Interestingly, the possible pathogenic mutation Q930R in LRRK2 drastically increases binding affinity to a peptide encompassing pS935. We then identified the autophosphorylation site T2524 as a so far not described 14-3-3 binding site at the very C-terminus of LRRK2. Binding affinities of all seven 14-3-3 isoforms were quantified for all three binding regions with pS1444 displaying the highest affinity of all measured singly phosphorylated peptides. The strongest binding was detected for the combined phosphosites S910 and S935, suggesting that avidity effects are important for high affinity interaction between 14-3-3 proteins and LRRK2.
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