LRRK2 Phosphorylation: Behind the Scenes

Parkinson's disease-associated mutant LRRK2 phosphorylates Rab7L1 and modifies trans-Golgi morphology

(2018) Tetta Fujimoto et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

GTP binding regulates cellular localization of Parkinson's disease-associated LRRK2

(2017) Marian Blanca Ramírez et al.   HUMAN MOLECULAR GENETICS

LRRK2 phosphorylates membrane-bound Rabs and is activated by GTP-bound Rab7L1 to promote recruitment to the trans-Golgi network

(2017) Zhiyong Liu et al.   HUMAN MOLECULAR GENETICS

T cells from patients with Parkinson’s disease recognize α-synuclein peptides

(2017) David Sulzer et al.   NATURE

A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci

(2017) Diana Chang et al.   NATURE GENETICS

Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

(2017) Martin Steger et al.   eLife

LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson’s Disease Mouse Model

(2017) Hien Tran Zhao et al.   Molecular Therapy-Nucleic Acids

Age-dependent dopamine transporter dysfunction and Serine129 phospho-α-synuclein overload in G2019S LRRK2 mice

(2017) Francesco Longo et al.   Acta Neuropathologica Communications

The discovery ofLRRK2p.R1441S, a novel mutation for Parkinson's disease, adds to the complexity of a mutational hotspot

(2016) Ignacio F. Mata et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS

Identification of protein phosphatase 2A as an interacting protein of leucine-rich repeat kinase 2

(2016) Panagiotis S. Athanasopoulos et al.   BIOLOGICAL CHEMISTRY

LRRK2 modulates microglial activity through regulation of chemokine (C–X3–C) receptor 1 –mediated signalling pathways

(2016) Bo Ma et al.   HUMAN MOLECULAR GENETICS

Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson's disease

(2016) Kyle B. Fraser et al.   MOVEMENT DISORDERS

LRRK2 levels and phosphorylation in Parkinson's disease brain and cases with restricted Lewy bodies

(2016) Nicolas Dzamko et al.   MOVEMENT DISORDERS

Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019SLRRK2carriers

(2016) Kyle B. Fraser et al.   NEUROLOGY

LRRK2 at the Crossroad Between Autophagy and Microtubule Trafficking

(2016) A. Raquel Esteves et al.   NEUROSCIENTIST

Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

(2016) Martin Steger et al.   eLife

Dysregulation of autophagy and mitochondrial function in Parkinson’s disease

(2016) Bao Wang et al.   Translational Neurodegeneration

Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation

(2016) E. Lobbestael et al.   Scientific Reports

LRRK2 and RAB7L1 coordinately regulate axonal morphology and lysosome integrity in diverse cellular contexts

(2016) Tomoki Kuwahara et al.   Scientific Reports

LRRK2 dephosphorylation increases its ubiquitination

(2015) Jing Zhao et al.   BIOCHEMICAL JOURNAL

The G2019S LRRK2 mutation increases myeloid cell chemotactic responses and enhances LRRK2 binding to actin-regulatory proteins

(2015) Mark S. Moehle et al.   HUMAN MOLECULAR GENETICS

14-3-3 Proteins regulate mutant LRRK2 kinase activity and neurite shortening

(2015) Nicholas J. Lavalley et al.   HUMAN MOLECULAR GENETICS

Leucine-rich Repeat Kinase 2 (LRRK2) Pharmacological Inhibition Abates α-Synuclein Gene-induced Neurodegeneration

(2015) João P. L. Daher et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Fine mapping and resequencing of the PARK16 locus in Parkinson’s disease

(2015) Lasse Pihlstrøm et al.   JOURNAL OF HUMAN GENETICS

Leucine-rich repeat kinase 2 positively regulates inflammation and down-regulates NF-κB p50 signaling in cultured microglia cells

(2015) Isabella Russo et al.   Journal of Neuroinflammation

LRRK2 A419V variant is a risk factor for Parkinson's disease in Asian population

(2015) Kai Li et al.   NEUROBIOLOGY OF AGING

Effect of selective LRRK2 kinase inhibition on nonhuman primate lung

(2015) Reina N. Fuji et al.   Science Translational Medicine

Leucine-Rich Repeat Kinase 2 (Lrrk2) Deficiency Diminishes the Development of Experimental Autoimmune Uveitis (EAU) and the Adaptive Immune Response

(2015) Wambui S. Wandu et al.   PLoS One

Leucine-rich repeat kinase 2 inhibitors: a review of recent patents (2011 – 2013)

(2014) Raghava R Kethiri et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

The chaperone-like protein 14-3-3η interacts with human α-synuclein aggregation intermediates rerouting the amyloidogenic pathway and reducing α-synuclein cellular toxicity

(2014) Nicoletta Plotegher et al.   HUMAN MOLECULAR GENETICS

Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy

(2014) J. Schapansky et al.   HUMAN MOLECULAR GENETICS

Pharmacological Treatment of Parkinson Disease

(2014) Barbara S. Connolly et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Arsenite Stress Down-regulates Phosphorylation and 14-3-3 Binding of Leucine-rich Repeat Kinase 2 (LRRK2), Promoting Self-association and Cellular Redistribution

(2014) Adamantios Mamais et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery and Preclinical Profiling of 3-[4-(Morpholin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile (PF-06447475), a Highly Potent, Selective, Brain Penetrant, and in Vivo Active LRRK2 Kinase Inhibitor

(2014) Jaclyn L. Henderson et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Role of LRRK2 in the Regulation of Monocyte Adhesion to Endothelial Cells

(2014) Li Hongge et al.   JOURNAL OF MOLECULAR NEUROSCIENCE

Interferon-γ induces leucine-rich repeat kinase LRRK2 via extracellular signal-regulated kinase ERK5 in macrophages

(2014) Martin Kuss et al.   JOURNAL OF NEUROCHEMISTRY

Differential protein-protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways

(2014) Lauran Reyniers et al.   JOURNAL OF NEUROCHEMISTRY

Mutant LRRK2 Toxicity in Neurons Depends on LRRK2 Levels and Synuclein But Not Kinase Activity or Inclusion Bodies

(2014) G. Skibinski et al.   JOURNAL OF NEUROSCIENCE

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

(2014) Mike A Nalls et al.   NATURE GENETICS

Lack of Correlation between the Kinase Activity of LRRK2 Harboring Kinase-Modifying Mutations and Its Phosphorylation at Ser910, 935, and Ser955

(2014) Genta Ito et al.   PLoS One

Abrogation of  -synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats

(2014) J. P. L. Daher et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

(2014) A. Beilina et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7

(2014) Ruth Chia et al.   Nature Communications

Immune Responses in Parkinson’s Disease: Interplay between Central and Peripheral Immune Systems

(2014) Xiaomin Su et al.   Biomed Research International

In silico, in vitro and cellular analysis with a kinome-wide inhibitor panel correlates cellular LRRK2 dephosphorylation to inhibitor activity on LRRK2

(2014) Renée Vancraenenbroeck et al.   Frontiers in Molecular Neuroscience

LRRK2 kinase activity and biology are not uniformly predicted by its autophosphorylation and cellular phosphorylation site status

(2014) April Reynolds et al.   Frontiers in Molecular Neuroscience

Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle

(2013) Evy Lobbestael et al.   BIOCHEMICAL JOURNAL

LRRK2 secretion in exosomes is regulated by 14-3-3

(2013) K. B. Fraser et al.   HUMAN MOLECULAR GENETICS

Evidence that the LRRK2 ROC domain Parkinson's disease-associated mutants A1442P and R1441C exhibit increased intracellular degradation

(2013) Izabella D. Greene et al.   JOURNAL OF NEUROSCIENCE RESEARCH

Population-specific frequencies forLRRK2susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium

(2013) Michael G. Heckman et al.   MOVEMENT DISORDERS

Interplay of LRRK2 with chaperone-mediated autophagy

(2013) Samantha J Orenstein et al.   NATURE NEUROSCIENCE

RAB7L1 Interacts with LRRK2 to Modify Intraneuronal Protein Sorting and Parkinson’s Disease Risk

(2013) David A. MacLeod et al.   NEURON

Loss of Leucine-Rich Repeat Kinase 2 (LRRK2) in Rats Leads to Progressive Abnormal Phenotypes in Peripheral Organs

(2013) Marco A. S. Baptista et al.   PLoS One

Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2 and disrupts its interaction with 14-3-3

(2013) K. Muda et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The G2385R variant of leucine-rich repeat kinase 2 associated with Parkinson's disease is a partial loss-of-function mutation

(2012) Iakov N. Rudenko et al.   BIOCHEMICAL JOURNAL

Phosphorylation of LRRK2: from kinase to substrate

(2012) Evy Lobbestael et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Leucine-rich repeat kinase 2 inhibitors: a patent review (2006 – 2011)

(2012) Xianming Deng et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Kinase inhibitors arrest neurodegeneration in cell and C. elegans models of LRRK2 toxicity

(2012) C. Yao et al.   HUMAN MOLECULAR GENETICS

LRRK2 Inhibition Attenuates Microglial Inflammatory Responses

(2012) M. S. Moehle et al.   JOURNAL OF NEUROSCIENCE

Development of an enzyme-linked immunosorbent assay for detection of cellular and in vivo LRRK2 S935 phosphorylation

(2012) Lore Delbroek et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

The link between the GBA gene and parkinsonism

(2012) Ellen Sidransky et al.   LANCET NEUROLOGY

Parkinson's disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity

(2012) F. Gillardon et al.   NEUROSCIENCE

Impaired Inflammatory Responses in Murine Lrrk2-Knockdown Brain Microglia

(2012) Beomsue Kim et al.   PLoS One

The IkappaB Kinase Family Phosphorylates the Parkinson’s Disease Kinase LRRK2 at Ser935 and Ser910 during Toll-Like Receptor Signaling

(2012) Nicolas Dzamko et al.   PLoS One

Screening for Novel LRRK2 Inhibitors Using a High-Throughput TR-FRET Cellular Assay for LRRK2 Ser935 Phosphorylation

(2012) Spencer B. Hermanson et al.   PLoS One

Ser1292 Autophosphorylation Is an Indicator of LRRK2 Kinase Activity and Contributes to the Cellular Effects of PD Mutations

(2012) Z. Sheng et al.   Science Translational Medicine

Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson's Disease

(2012) O. Cooper et al.   Science Translational Medicine

Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database

(2012) Christina M. Lill et al.   PLoS Genetics

LRRK2 in Transcription and Translation Regulation: Relevance for Parkinson’s Disease

(2012) Véronique Dorval et al.   Frontiers in Neurology

LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice

(2011) Martin C. Herzig et al.   HUMAN MOLECULAR GENETICS

LRRK2 Parkinson disease mutations enhance its microtubule association

(2011) Lauren R. Kett et al.   HUMAN MOLECULAR GENETICS

Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning

(2011) M. W. Dodson et al.   HUMAN MOLECULAR GENETICS

Autophosphorylation in the Leucine-Rich Repeat Kinase 2 (LRRK2) GTPase Domain Modifies Kinase and GTP-Binding Activities

(2011) Philip J. Webber et al.   JOURNAL OF MOLECULAR BIOLOGY

Parkinson’s disease-linked LRRK2 is expressed in circulating and tissue immune cells and upregulated following recognition of microbial structures

(2011) Mansoureh Hakimi et al.   JOURNAL OF NEURAL TRANSMISSION

Phosphorylation of LRRK2 serines 955 and 973 is disrupted by Parkinson’s disease mutations and LRRK2 pharmacological inhibition

(2011) Elizabeth A. Doggett et al.   JOURNAL OF NEUROCHEMISTRY

LRRK2: A Problem Lurking in Vesicle Trafficking?

(2011) S. Dihanich et al.   JOURNAL OF NEUROSCIENCE

Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case–control study

(2011) Owen A Ross et al.   LANCET NEUROLOGY

Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2

(2011) Xianming Deng et al.   Nature Chemical Biology

The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease

(2011) Zhihua Liu et al.   NATURE IMMUNOLOGY

Phosphorylation-Dependent 14-3-3 Binding to LRRK2 Is Impaired by Common Mutations of Familial Parkinson's Disease

(2011) Xianting Li et al.   PLoS One

Regulation of LRRK2 Expression Points to a Functional Role in Human Monocyte Maturation

(2011) Jonathan Thévenet et al.   PLoS One

Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser910/Ser935, disruption of 14-3-3 binding and altered cytoplasmic localization

(2010) Nicolas Dzamko et al.   BIOCHEMICAL JOURNAL

14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization

(2010) R. Jeremy Nichols et al.   BIOCHEMICAL JOURNAL

Membrane Localization of LRRK2 Is Associated with Increased Formation of the Highly Active LRRK2 Dimer and Changes in Its Phosphorylation

(2010) Zdenek Berger et al.   BIOCHEMISTRY

LRRK2 Is Involved in the IFN-  Response and Host Response to Pathogens

(2010) A. Gardet et al.   JOURNAL OF IMMUNOLOGY

LRRK2 is expressed in B-2 but not in B-1 B cells, and downregulated by cellular activation

(2010) Makoto Kubo et al.   JOURNAL OF NEUROIMMUNOLOGY

LRRK2 Kinase Regulates Synaptic Morphology through Distinct Substrates at the Presynaptic and Postsynaptic Compartments of the Drosophila Neuromuscular Junction

(2010) S. Lee et al.   JOURNAL OF NEUROSCIENCE

Phosphopeptide Analysis Reveals Two Discrete Clusters of Phosphorylation in the N-Terminus and the Roc Domain of the Parkinson-Disease Associated Protein Kinase LRRK2

(2010) Christian Johannes Gloeckner et al.   JOURNAL OF PROTEOME RESEARCH

Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease

(2010) Byoung Dae Lee et al.   NATURE MEDICINE

Identification and Characterization of a Leucine-Rich Repeat Kinase 2 (LRRK2) Consensus Phosphorylation Motif

(2010) Pooja P. Pungaliya et al.   PLoS One

Differential neuroprotective effects of 14-3-3 proteins in models of Parkinson's disease

(2010) T A Yacoubian et al.   Cell Death & Disease

Leucine-Rich Repeat Kinase 2 Mutations and Parkinson's Disease: Three Questions

(2009) Elisa Greggio et al.   ASN Neuro

I2020T leucine-rich repeat kinase 2, the causative mutant molecule of familial Parkinson’s disease, has a higher intracellular degradation rate than the wild-type molecule

(2009) Etsuro Ohta et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease

(2009) R. Jeremy Nichols et al.   BIOCHEMICAL JOURNAL

LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model

(2009) Javier Alegre-Abarrategui et al.   HUMAN MOLECULAR GENETICS

Molecular Pathology of Lewy Body Diseases

(2009) Katrin Beyer et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Dependence of Leucine-rich Repeat Kinase 2 (LRRK2) Kinase Activity on Dimerization

(2009) Saurabh Sen et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease

(2009) Wataru Satake et al.   NATURE GENETICS

Genome-wide association study reveals genetic risk underlying Parkinson's disease

(2009) Javier Simón-Sánchez et al.   NATURE GENETICS

Leucine-Rich Repeat Kinase 2 Regulates the Progression of Neuropathology Induced by Parkinson's-Disease-Related Mutant α-synuclein

(2009) Xian Lin et al.   NEURON

Clinical features of LRRK2 parkinsonism

(2009) Kristoffer Haugarvoll et al.   PARKINSONISM & RELATED DISORDERS

The WD40 Domain Is Required for LRRK2 Neurotoxicity

(2009) Nathan D. Jorgensen et al.   PLoS One

Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease

(2008) Owen A. Ross et al.   ANNALS OF NEUROLOGY

Non-motor symptoms in Parkinson’s disease

(2008) W. Poewe   EUROPEAN JOURNAL OF NEUROLOGY

The Parkinson Disease-associated Leucine-rich Repeat Kinase 2 (LRRK2) Is a Dimer That Undergoes Intramolecular Autophosphorylation

(2008) Elisa Greggio et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Chaperone Activity of Heat Shock Protein 90 Is Critical for Maintaining the Stability of Leucine-Rich Repeat Kinase 2

(2008) L. Wang et al.   JOURNAL OF NEUROSCIENCE

Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study

(2008) Daniel G Healy et al.   LANCET NEUROLOGY

Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease

(2008) K. Haugarvoll et al.   NEUROLOGY

Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase

(2008) J. Deng et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA