ArticleExperimental cell research2007
The Parkinson's disease-associated protein, leucine-rich repeat kinase 2 (LRRK2), is an authentic GTPase that stimulates kinase activity.
Article in Experimental cell research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
115 citing papers in PubMed, 209 citations in OpenAlex.
- Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non-Hodgkin lymphoma.British journal of haematology · 2019Trial
- Article
- The structural basis for LRRK2's activation and autoinhibition.bioRxiv : the preprint server for biology · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Structural biology of Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2).The Journal of biological chemistry · 2025Review
- LRRK2 kinase inhibition protects against Parkinson's disease-associated environmental toxicants.Neurobiology of disease · 2024Article
- New Pyrrolopyrimidines as LRRK2 Inhibitors for Treating Parkinson's Disease.Current medicinal chemistry · 2024Article
- Review
- Leucine-rich repeat kinase 2 at a glance.Journal of cell science · 2023Article
- LRRK2 phosphorylation status and kinase activity regulate (macro)autophagy in a Rab8a/Rab10-dependent manner.Cell death & disease · 2023Article
- Overview of the Impact of Pathogenic LRRK2 Mutations in Parkinson's Disease.Biomolecules · 2023Review
- Rotenone-Induced Model of Parkinson's Disease: Beyond Mitochondrial Complex I Inhibition.Molecular neurobiology · 2023Review
- Roc, the G-domain of the Parkinson's disease-associated protein LRRK2.Trends in biochemical sciences · 2022Review
- Homozygous mutation of the LRRK2 ROC domain as a novel genetic model of parkinsonism.Journal of biomedical science · 2022Article
- Kinases on Double Duty: A Review of UniProtKB Annotated Bifunctionality within the Kinome.Biomolecules · 2022Review
- Genetic variations inFrontiers in neurology · 2022Review
- Structural Biology of LRRK2 and its Interaction with Microtubules.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain.PLoS genetics · 2021Article
- Fluctuation Imaging of LRRK2 Reveals that the G2019S Mutation Alters Spatial and Membrane Dynamics.Molecules (Basel, Switzerland) · 2020Article
- Allosteric modulation of the GTPase activity of a bacterial LRRK2 homolog by conformation-specific Nanobodies.The Biochemical journal · 2020Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the leading cause of autosomal dominant Parkinson's disease (PD). LRRK2, a member of the ROCO protein family, contains both Ras GTPase-like (Roc) and kinase (MAPKKK) domains, as well as other functional motifs. Here, we have identified LRRK2 as the first mammalian ROCO protein that is an authentic and functional GTPase, defined by the ability to bind GTP and undergo intrinsic GTP hydrolysis. Furthermore, the Roc domain is sufficient for this native GTPase activity and binds and hydrolyzes GTP indistinguishably from the Ras-related small GTPase, Rac1. The PD-associated mutation, R1441C, located within the Roc domain, leads to an increase in LRRK2 kinase activity and a decrease in the rate of GTP hydrolysis, compared to the wild-type protein, in an in vitro assay. This finding suggests that the R1441C mutation may help stabilize an activated state of LRRK2. Additionally, LRRK2-mediated phosphorylation is stimulated upon binding of non-hydrolyzable GTP analogs, suggesting that LRRK2 is an MAPKKK-activated intramolecularly by its own GTPase. Since GTPases and MAPKKKs are upstream regulators of multiple signal transduction cascades, LRRK2 may play a central role in integrating pathways involved in neuronal cell signaling and the pathogenesis of PD.
Indexed as
Identifiers
What OpenQuestion holds
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.