Rabbit monoclonal [UDD1 15(3)] to LRRK2 (phospho S910)
WBmore details Unsuitable for:
Flow Cyt,ICC/IF,IHC-P or IP
Synthetic phosphopeptide corresponding to a region surrounding Serine 910 of Human LRRK2 (UniProt Q5S007).
GFP-LRRK2 lysate and Lymphoblastoid lysate
This product is a recombinant rabbit monoclonal antibody.
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.
Mouse: We have preliminary internal testing data to indicate this antibody may not react with these species. Please contact us for more information.
Our RabMAb® technology is a patented hybridoma-based technology for making rabbit monoclonal antibodies. For details on our patents, please refer to RabMab® patents
Shipped at 4°C. Store at -20°C. Stable for 12 months at -20°C.
The application notes include recommended starting dilutions; optimal dilutions/concentrations should be determined by the end user.
1/1000 - 1/5000. Detects a band of approximately 286 kDa (predicted molecular weight: 286 kDa).
Is unsuitable for Flow Cyt,ICC/IF,IHC-P or IP.
Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. 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. Regulates neuronal process morphology in the intact central nervous system (CNS). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease.
Expressed in the brain. Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level). Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas.
Involvement in disease
Parkinson disease 8
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Contains 12 LRR (leucine-rich) repeats. Contains 1 protein kinase domain. Contains 1 Roc domain. Contains 7 WD repeats.
The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins. The Roc domain mediates homodimerization and regulates kinase activity.
Membrane. Cytoplasm. Perikaryon. Mitochondrion. Golgi apparatus. Cell projection, axon. Cell projection, dendrite. Endoplasmic reticulum. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane. Endosome. Lysosome. Mitochondrion outer membrane. Mitochondrion inner membrane. Mitochondrion matrix. Predominantly associated with intracytoplasmic vesicular and membranous structures (By similarity). Localized in the cytoplasm and associated with cellular membrane structures. Predominantly associated with the mitochondrial outer membrane of the mitochondria. Colocalized with RAB29 along tubular structures emerging from Golgi apparatus. Localizes in intracytoplasmic punctate structures of neuronal perikarya and dendritic and axonal processes.
Western blot - Anti-LRRK2 (phospho S910) antibody [UDD1 15(3)] (ab133449)
All lanes : 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 Lane 4 : Lymphoblastoid lysate at 30 µg Lane 5 : Lymphoblastoid lysate at 30 µg Lane 6 : Lymphoblastoid lysate from
LRRK2 IN1 treated cells at 30 µg Lane 7 : Lymphoblastoid lysate from
LRRK2 IN1 treated cells at 30 µg
Secondary HRP conjugated goat anti-rabbit antibody at 1/2000 dilution
Perera G et al. Inhibitor treatment of peripheral mononuclear cells from Parkinson's disease patients further validates LRRK2 dephosphorylation as a pharmacodynamic biomarker. Sci Rep6:31391 (2016).
Read more (PubMed: 27503089) »
Ito G et al. Lack of correlation between the kinase activity of LRRK2 harboring kinase-modifying mutations and its phosphorylation at Ser910, 935, and Ser955. PLoS One9:e97988 (2014).
Read more (PubMed: 24836358) »