Evidence map›Paper›PMID 29127256›Full record

ArticleThe Biochemical journal2018

Development of phospho-specific Rab protein antibodies to monitor

Pawel Lis, Sophie Burel, Martin Steger, Matthias Mann, Fiona Brown, Federico Diez, Francesca Tonelli, Janice L Holton, Philip Winglok Ho, Shu-Leong Ho and 5 more

Open access · hybridAbstract read
In one paragraph

Article in The Biochemical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
10.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

91 citing papers in PubMed, 165 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Functional and Structural Characterization of LRRK2 p.V1447L in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025
    Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. 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 · 2025
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

31 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 2 countries.

Pawel LisMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. p.lis@dundee.ac.uk d.r.alessi@dundee.ac.uk.
Sophie BurelMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Martin StegerDepartment of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Matthias MannDepartment of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Fiona BrownMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Federico DiezMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Francesca TonelliMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Janice L HoltonDivision of Neuropathology, UCL Institute of Neurology, Queen Square, London, U.K.
Philip Winglok HoDivision of Neurology, Department of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong.
Shu-Leong HoDivision of Neurology, Department of Medicine, University of Hong Kong, Pok Fu Lam, Hong Kong.
Meng-Yun ChouAbcam, 863 Mitten Rd, Burlingame, CA 94010, U.S.A.
Nicole K PolinskiThe Michael J. Fox Foundation for Parkinson's Research, Grand Central Station, PO Box 4777, New York, NY 10163, U.S.A.
Terina N MartinezThe Michael J. Fox Foundation for Parkinson's Research, Grand Central Station, PO Box 4777, New York, NY 10163, U.S.A.
Paul DaviesMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Dario R AlessiMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. p.lis@dundee.ac.uk d.r.alessi@dundee.ac.uk.
Max Planck Institute of Biochemistry · DEUniversity of Hong Kong · HK

Funding

Medical Research Council G0700656Medical Research Council MC_U127070193Medical Research Council MC_UU_00018/1Medical Research Council MC_UU_12016/2Medical Research Council MR/P00704X/1Parkinson's UK H-1701
6 · The paper itself

Abstract

Mutations that activate the LRRK2 (leucine-rich repeat protein kinase 2) protein kinase predispose to Parkinson's disease, suggesting that LRRK2 inhibitors might have therapeutic benefit. Recent work has revealed that LRRK2 phosphorylates a subgroup of 14 Rab proteins, including Rab10, at a specific residue located at the centre of its effector-binding switch-II motif. In the present study, we analyse the selectivity and sensitivity of polyclonal and monoclonal phospho-specific antibodies raised against nine different LRRK2-phosphorylated Rab proteins (Rab3A/3B/3C/3D, Rab5A/5B/5C, Rab8A/8B, Rab10, Rab12, Rab29[T71], Rab29[S72], Rab35 and Rab43). We identify rabbit monoclonal phospho-specific antibodies (MJFF-pRAB10) that are exquisitely selective for LRRK2-phosphorylated Rab10, detecting endogenous phosphorylated Rab10 in all analysed cell lines and tissues, including human brain cingulate cortex. We demonstrate that the MJFF-pRAB10 antibodies can be deployed to assess enhanced Rab10 phosphorylation resulting from pathogenic (R1441C/G or G2019S) LRRK2 knock-in mutations as well as the impact of LRRK2 inhibitor treatment. We also identify rabbit monoclonal antibodies displaying broad specificity (MJFF-pRAB8) that can be utilised to assess LRRK2-controlled phosphorylation of a range of endogenous Rab proteins, including Rab8A, Rab10 and Rab35. The antibodies described in the present study will help with the assessment of LRRK2 activity and examination of which Rab proteins are phosphorylated

Indexed as

MutationAmino Acid SequenceAnimalsAntibodies, MonoclonalAntibodies, Phospho-SpecificAntibody SpecificityGene Expression RegulationGenetic Predisposition to DiseaseGyrus CinguliHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MiceMultigene FamilyParkinson DiseasePhosphorylationProtein IsoformsAntibodies, MonoclonalAntibodies, Phospho-SpecificLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanProtein IsoformsRab10 protein, humanRAB8A protein, humanrab GTP-Binding Proteinsantibodiesleucine-rich repeat kinaseParkinson's diseaseprotein kinaseRab10Rab GTPases

Identifiers

PMID29127256
PMCPMC5748839
OpenAlexW2767998367

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.