ArticleThe Biochemical journal2020
PINK1-dependent phosphorylation of Serine111 within the SF3 motif of Rab GTPases impairs effector interactions and LRRK2-mediated phosphorylation at Threonine72.
Article in The Biochemical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 40 citations in OpenAlex.
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.Nature communications · 2026Article
- Rab8a dysregulation in Parkinson's disease: A convergence of genetic and molecular pathologies.Molecular biology reports · 2026Review
- Selectivity profiles and substrate recognition of Rab-phosphorylating kinases.The Biochemical journal · 2025Article
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.bioRxiv : the preprint server for biology · 2025Article
- A new LRRK2 variant in a family with Parkinson's disease affects binding to RAB8A.NPJ Parkinson's disease · 2025Article
- Kinome screening identifies integrated stress response kinase EIF2AK1/HRI as a negative regulator of PINK1 mitophagy signaling.Science advances · 2025Article
- Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanism of human PINK1 activation at the TOM complex in a reconstituted system.Science advances · 2024Article
- Genetic Encoding of Phosphorylated Amino Acids into Proteins.Chemical reviews · 2024Review
- The LRRK2 kinase substrates RAB8a and RAB10 contribute complementary but distinct disease-relevant phenotypes in human neurons.Stem cell reports · 2024Article
- Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease, with insights intoZoological research · 2023Review
- The Role of Rab Proteins in Mitophagy: Insights into Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Accessing isotopically labeled proteins containing genetically encoded phosphoserine for NMR with optimized expression conditions.The Journal of biological chemistry · 2022Article
- Article
- Nuclear and Cytoplasmatic Players in Mitochondria-Related CNS Disorders: Chromatin Modifications and Subcellular Trafficking.Biomolecules · 2022Review
- The Regulation of Rab GTPases by Phosphorylation.Biomolecules · 2021Review
- Genetic background influences LRRK2-mediated Rab phosphorylation in the rat brain.Brain research · 2021Article
- Preclinical modeling of chronic inhibition of the Parkinson's disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo.Molecular neurodegeneration · 2021Article
- The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease.International journal of molecular sciences · 2021Review
- Mitochondrial Function and Parkinson's Disease: From the Perspective of the Electron Transport Chain.Frontiers in molecular neuroscience · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Loss of function mutations in the PTEN-induced kinase 1 (PINK1) kinase are causal for autosomal recessive Parkinson's disease (PD) whilst gain of function mutations in the LRRK2 kinase cause autosomal dominant PD. PINK1 indirectly regulates the phosphorylation of a subset of Rab GTPases at a conserved Serine111 (Ser111) residue within the SF3 motif. Using genetic code expansion technologies, we have produced stoichiometric Ser111-phosphorylated Rab8A revealing impaired interactions with its cognate guanine nucleotide exchange factor and GTPase activating protein. In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. Strikingly, we demonstrate that Ser111 phosphorylation negatively regulates the ability of LRRK2 but not MST3 or TAK1 to phosphorylate Thr72 of recombinant nucleotide-bound Rab8A in vitro and demonstrate an interplay of PINK1- and LRRK2-mediated phosphorylation of Rab8A in transfected HEK293 cells. Finally, we present the crystal structure of Ser111-phosphorylated Rab8A and nuclear magnetic resonance structure of Ser111-phosphorylated Rab1B. The structures reveal that the phosphorylated SF3 motif does not induce any major changes, but may interfere with effector-Switch II interactions through intramolecular H-bond formation and/or charge effects with Arg79. Overall, we demonstrate antagonistic regulation between PINK1-dependent Ser111 phosphorylation and LRRK2-mediated Thr72 phosphorylation of Rab8A indicating a potential cross-talk between PINK1-regulated mitochondrial homeostasis and LRRK2 signalling that requires further investigation in vivo.
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.