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AB133449

Anti-LRRK2 (phospho S910) antibody [UDD1 15(3)]

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(15 Publications)

Rabbit Recombinant Monoclonal LRRK2 phospho S910 antibody. Suitable for WB and reacts with Human samples. Cited in 15 publications.

View Alternative Names

PARK8, LRRK2, Leucine-rich repeat serine/threonine-protein kinase 2, Dardarin

2 Images
Western blot - Anti-LRRK2 (phospho S910) antibody [UDD1 15(3)] (AB133449)
  • WB

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Western blot - Anti-LRRK2 (phospho S910) antibody [UDD1 15(3)] (AB133449)

All lanes:

Western blot - Anti-LRRK2 (phospho S910) antibody [UDD1 15(3)] (ab133449) at 1/1000 dilution

Lane 1:

GFP tagged WT LRRK2 lysate at 5 µg

Lane 2:

GFP LRRK2 S910A lysate at 5 µg

Lane 3:

GFP LRRK2 S935A lysate at 5 µg

Lanes 4 - 5:

Lymphoblastoid lysate at 30 µg

Lanes 6 - 7:

Lymphoblastoid lysate from LRRK2 IN1 treated cells at 30 µg

Secondary

All lanes:

HRP conjugated goat anti-rabbit antibody at 1/2000 dilution

Predicted band size: 286 kDa

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Western blot - Anti-LRRK2 (phospho S910) antibody [UDD1 15(3)] (AB133449)
  • WB

CiteAb

Western blot - Anti-LRRK2 (phospho S910) antibody [UDD1 15(3)] (AB133449)

LRRK2 (phospho S910) western blot using anti-LRRK2 (phospho S910) antibody [UDD1 15(3)] ab133449. Publication image and figure legend from Chia, R., Haddock, S., et al., 2014, Nat Commun, PubMed 25500533.

ab133449 was used in this publication in western blot. This may not be the same as the application(s) guaranteed by Abcam. For a full list of applications guaranteed by Abcam for ab133449 please see the product overview.

CK1α directly phosphorylates LRRK2 in vitro and in vivoa) LRRK2 is a substrate of CK1α. CK1α phosphorylates LRRK2, in vitro, at S910, S935, S955 and S973 sites. Representative blots of 3 independent experiments.b) Consensus sequence of CK1 phosphorylation. The S/Tp-X-X-S/T is the canonical phosphorylation motif42. Alternative phosphorylation motif of CK1 consist of an SLS motif followed by an acidic cluster in positions n+7 (underlined43). Sequence analysis of LRRK2 shows that serines 910, 935 and other constitutively phosphorylated serines at 973/975/976 is a weak consensus site for canonical and non-canonical CK1α phosphorylation. Phosphorylated serines of LRRK2 are shown in red.c) IC261 but not LRRK2-IN1, inhibited CK1α phosphorylation of LRRK2 in vitro. Concentrations of inhibitors used were 50 mM IC261 and 100 nM LRRK2-IN1. Results were consistent even when higher concentration of inhibitor, 100 mM IC261 and 1 μM LRRK2-IN1, was used (Supplementary Fig. 4b). Representative blots of 3 independent experiments.d) Quantitation of blots in 3c. Graph shows mean +/- SEM. Statistical significance tested with two-way ANOVA with Bonferroni post-hoc test (* p<0.05; ** p<0.01; n.s. = not significant).e) LRRK2 is dephosphorylated at S910, S935, S955 and S973 upon knockdown with CSNK1A1 siRNA in a LRRK2-kinase independent manner, as both WT and K1906M is dephosphorylated to the same extent.f) CSNK1A1 siRNA knockdown samples described in 3e were subjected to LC-MS/MS analysis for phospho-peptide mapping. The XIC peak area extracted from the LC-MS/MS data was used to calculate the relative abundance of the detected phospho-peptide in different conditions. Graph shows the quantitative loss of ~70–80%, of pS908, pS910, pS935, pS955, pS973 and pS976 from CSNK1A1 compared to NTC siRNA samples for both WT (filled circles) and K1906M (open circles).

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  • Carrier free

    Anti-LRRK2 (phospho S910) antibody [UDD1 15(3)] - BSA and Azide free

Key facts

Host species

Rabbit

Clonality

Monoclonal

Clone number

UDD1 15(3)

Isotype

IgG

Carrier free

No

Reacts with

Human

Applications

WB

applications

Immunogen

The exact immunogen used to generate this antibody is proprietary information.

Reactivity data

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Product details

This antibody was developed with the support of The Michael J. Fox Foundation (MJFF) and in partnership with Dr. Dario Alessi (MRC Protein Phosphorylation Unit, University of Dundee) to help accelerate LRRK2 research. Dr. Alessi has characterized several unique and high quality LRRK2 rabbit monoclonal antibodies, generated by Abcam, to be made widely available for PD research community.

LRRK2 (Leucine-rich repeat kinase 2, dardarin) is a multi-domain protein belonging to the ROCO family of proteins that contains a kinase and GTPase domain among its many protein interaction domains. LRRK2 is mutated in a significant number of Parkinson's disease (PD) patients. Mutations in this gene account for 4% of PD, and are observed in 1% of sporadic PD patients. The most common mutation replaces glycine 2019 with a serine that results in increased LRRK2 kinase activity. This indicates that inhibitors of LRRK2 kinase activity might be of therapeutic benefit for the treatment of Parkinson's disease and has stimulated much activity in this field of research.

Recent work has revealed that LRRK2 interacts with14-3-3 phospho-binding adaptor isoforms that is mediated by phosphorylation of Ser910 and Ser935 located prior to the leucine rich repeat domain mediates. Interestingly, 14-3-3 binding has been linked to Parkinson's disease as Ser910 as well as Ser935 and interaction with the 14-3-3 is inhibited by five of the six validated LRRK2 pathogenic mutations (R1441C, R1441G, R1441H, Y1699C and I2020T). The Dundee-MJFF LRRK2 PhosphoSer935 antibody will be of great utility in further understanding the link between 14-3-3 binding to LRRK2 and Parkinson's disease as well as assessing the efficacy of LRRK2 inhibitors that are being developed.

It should be noted the Dundee-MJFF antibody is highly selective and sensitive and can readily be used to monitor LRRK2 Ser910 phosphorylation in immunoblot analysis of 2-20 microgram amounts of whole cell extract. The Dundee-MJFF LRRK2 PhosphoSer910 recognizes human but not mouse endogenous LRRK2.

Species reactivity
Mouse: We have preliminary internal testing data to indicate this antibody may not react with this species.
Please contact us for more information.

Patented technology
Our RabMAb® technology is a patented hybridoma-based technology for making rabbit monoclonal antibodies. For details on our patents, please refer to RabMAb® patents.

What are the advantages of a recombinant monoclonal antibody?
This product is a recombinant monoclonal antibody, which offers several advantages including:

  • - High batch-to-batch consistency and reproducibility
  • - Improved sensitivity and specificity
  • - Long-term security of supply
  • - Animal-free batch production

For more information, read more on recombinant antibodies.

Collaborations
This antibody was developed with support from The Michael J. Fox Foundation.

Properties and storage information

Form
Liquid
Purification technique
Affinity purification Protein A
Storage buffer
pH: 7.2 - 7.4 Preservative: 0.01% Sodium azide Constituents: PBS, 40% Glycerol (glycerin, glycerine), 0.05% BSA
Shipped at conditions
Blue Ice
Appropriate short-term storage conditions
+4°C
Appropriate long-term storage conditions
-20°C
Storage information
Stable for 12 months at -20°C

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

The protein LRRK2 also known as leucine-rich repeat kinase 2 or dardarin is an enzyme with a molecular weight of approximately 286 kDa. It functions as a kinase meaning it adds phosphate groups to other proteins which affects their activity. LRRK2 is expressed in various tissues but it is highly abundant in the brain especially in regions such as the striatum and cortex. It has a significant role in cellular signaling processes due to its phosphorylation activity.
Biological function summary

LRRK2 interacts with cellular mechanisms by regulating cytoskeletal dynamics autophagy and vesicle trafficking. It is a part of a larger complex that includes other proteins involved in these processes. The kinase activity of LRRK2 plays an essential part in maintaining neuronal health and function. It influences the process of autophagy which is a way cells clean themselves by removing damaged components and recycling them.

Pathways

The action of LRRK2 is central to the mitogen-activated protein kinase (MAPK) and the mammalian target of rapamycin (mTOR) pathways. In these pathways LRRK2 interacts with other proteins such as mTOR and RPS6KB1. It modulates cellular processes like growth proliferation and response to stressors. Its kinase activity affects the phosphorylation state of targets within the pathways hence influencing biological outcomes like survival and apoptosis.

LRRK2 mutations have a significant connection to Parkinson's disease and Crohn's disease. In Parkinson's disease mutated LRRK2 leads to abnormal protein aggregation linking to proteins such as alpha-synuclein. For Crohn's disease LRRK2 influences the immune response and intestinal inflammation. These connections highlight LRRK2's role in the pathogenesis and contribute to understanding these complex disorders.

Product protocols

For this product, it's our understanding that no specific protocols are required. You can visit:

Target data

Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed : 17114044, PubMed : 20949042, PubMed : 21850687, PubMed : 22012985, PubMed : 23395371, PubMed : 24687852, PubMed : 25201882, PubMed : 26014385, PubMed : 26824392, PubMed : 27830463, PubMed : 28720718, PubMed : 29125462, PubMed : 29127255, PubMed : 29212815, PubMed : 30398148, PubMed : 30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed : 26824392, PubMed : 28720718, PubMed : 29125462, PubMed : 29127255, PubMed : 29212815, PubMed : 30398148, PubMed : 30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed : 23395371, PubMed : 26824392, PubMed : 28720718, PubMed : 29125462, PubMed : 29127255, PubMed : 29212815, PubMed : 30398148, PubMed : 30635421, PubMed : 38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed : 26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed : 26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed : 29125462, PubMed : 30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed : 23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed : 17114044). Plays a role in synaptic vesicle trafficking (PubMed : 24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed : 25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed : 22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed : 22012985). Phosphorylates PRDX3 (PubMed : 21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed : 28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed : 27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed : 26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed : 18230735, PubMed : 26824392, PubMed : 28720718, PubMed : 29125462, PubMed : 29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed : 30209220, PubMed : 38227290).
See full target information LRRK2 phospho S910

Publications (15)

Recent publications for all applications. Explore the full list and refine your search

NPJ Parkinson's disease 9:21 PubMed36750568

2023

Alterations in the LRRK2-Rab pathway in urinary extracellular vesicles as Parkinson's disease and pharmacodynamic biomarkers.

Applications

Unspecified application

Species

Unspecified reactive species

Jean-Marc Taymans,Eugénie Mutez,William Sibran,Laurine Vandewynckel,Claire Deldycke,Séverine Bleuse,Antoine Marchand,Alessia Sarchione,Coline Leghay,Alexandre Kreisler,Clémence Simonin,James Koprich,Guillaume Baille,Luc Defebvre,Kathy Dujardin,Alain Destée,Marie-Christine Chartier-Harlin

Molecular brain 16:2 PubMed36604743

2023

14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson's disease-like motor incoordination in mice.

Applications

Unspecified application

Species

Unspecified reactive species

Eunsil Cho,Jinsil Park,Eun Mi Hwang,Hyung Wook Kim,Jae-Yong Park

The Journal of cell biology 221: PubMed35266954

2022

The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.

Applications

Unspecified application

Species

Unspecified reactive species

Adrienne E D Stormo,Farbod Shavarebi,Molly FitzGibbon,Elizabeth M Earley,Hannah Ahrendt,Lotus S Lum,Erik Verschueren,Danielle L Swaney,Gaia Skibinski,Abinaya Ravisankar,Jeffrey van Haren,Emily J Davis,Jeffrey R Johnson,John Von Dollen,Carson Balen,Jacob Porath,Claudia Crosio,Christian Mirescu,Ciro Iaccarino,William T Dauer,R Jeremy Nichols,Torsten Wittmann,Timothy C Cox,Steve Finkbeiner,Nevan J Krogan,Scott A Oakes,Annie Hiniker

Clinical and translational medicine 11:e341 PubMed33784003

2021

LRRK2 inhibition potentiates PARP inhibitor cytotoxicity through inhibiting homologous recombination-mediated DNA double strand break repair.

Applications

Unspecified application

Species

Unspecified reactive species

Lifeng Chen,Jing Hou,Xiangyu Zeng,Qiang Guo,Min Deng,Jake A Kloeber,Xinyi Tu,Fei Zhao,Zheming Wu,Jinzhou Huang,Kuntian Luo,Wootae Kim,Zhenkun Lou

Scientific reports 10:17293 PubMed33057100

2020

Mitochondrial DNA damage as a potential biomarker of LRRK2 kinase activity in LRRK2 Parkinson's disease.

Applications

Unspecified application

Species

Unspecified reactive species

C P Gonzalez-Hunt,E A Thacker,C M Toste,S Boularand,S Deprets,L Dubois,L H Sanders

Proceedings of the National Academy of Sciences of 116:14979-14988 PubMed31292254

2019

The dynamic switch mechanism that leads to activation of LRRK2 is embedded in the DFGψ motif in the kinase domain.

Applications

Unspecified application

Species

Unspecified reactive species

Sven H Schmidt,Matthias J Knape,Daniela Boassa,Natascha Mumdey,Alexandr P Kornev,Mark H Ellisman,Susan S Taylor,Friedrich W Herberg

Nature communications 9:3465 PubMed30150626

2018

LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation.

Applications

Unspecified application

Species

Unspecified reactive species

Eun-Jin Bae,Dong-Kyu Kim,Changyoun Kim,Michael Mante,Anthony Adame,Edward Rockenstein,Ayse Ulusoy,Michael Klinkenberg,Ga Ram Jeong,Jae Ryul Bae,Cheolsoon Lee,He-Jin Lee,Byung-Dae Lee,Donato A Di Monte,Eliezer Masliah,Seung-Jae Lee

The EMBO journal 37:1-18 PubMed29212815

2017

Rab29 activation of the Parkinson's disease-associated LRRK2 kinase.

Applications

Unspecified application

Species

Unspecified reactive species

Elena Purlyte,Herschel S Dhekne,Adil R Sarhan,Rachel Gomez,Pawel Lis,Melanie Wightman,Terina N Martinez,Francesca Tonelli,Suzanne R Pfeffer,Dario R Alessi

Human molecular genetics 26:4494-4505 PubMed28973420

2017

LRRK2 interacts with ATM and regulates Mdm2-p53 cell proliferation axis in response to genotoxic stress.

Applications

Unspecified application

Species

Unspecified reactive species

Zhongcan Chen,Zhen Cao,Wei Zhang,Minxia Gu,Zhi Dong Zhou,Baojie Li,Jing Li,Eng King Tan,Li Zeng

Scientific reports 6:31391 PubMed27503089

2016

Inhibitor treatment of peripheral mononuclear cells from Parkinson's disease patients further validates LRRK2 dephosphorylation as a pharmacodynamic biomarker.

Applications

Unspecified application

Species

Unspecified reactive species

G Perera,M Ranola,D B Rowe,G M Halliday,N Dzamko
View all publications

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