LRRK2 Phosphorylation, More Than an Epiphenomenon

The In situ Structure of Parkinson's Disease-Linked LRRK2

(2020) Reika Watanabe et al.   BIOPHYSICAL JOURNAL

Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-present)

(2020) Xiao Ding et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

An Assessment of LRRK2 Serine 935 Phosphorylation in Human Peripheral Blood Mononuclear Cells in Idiopathic Parkinson’s Disease and G2019S LRRK2 Cohorts

(2020) Shalini Padmanabhan et al.   Journal of Parkinsons Disease

Kinase activity of mutant LRRK2 manifests differently in hetero-dimeric vs homo-dimeric complexes

(2019) Emmanouela Leandrou et al.   BIOCHEMICAL JOURNAL

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

(2019) Sven H. Schmidt et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Centrosomal cohesion deficits as cellular biomarker in lymphoblastoid cell lines from LRRK2 Parkinson's disease patients

(2019) Belén Fernández et al.   BIOCHEMICAL JOURNAL

Identification of PP2A and S6 Kinase as Modifiers of Leucine-Rich Repeat Kinase-Induced Neurotoxicity

(2019) Joan Poh Ling Sim et al.   NEUROMOLECULAR MEDICINE

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

(2019) Mike A Nalls et al.   LANCET NEUROLOGY

P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity

(2018) Alexia F. Kalogeropulou et al.   BIOCHEMICAL JOURNAL

Comparative Protein Interaction Network Analysis Identifies Shared and Distinct Functions for the Human ROCO Proteins

(2018) James E. Tomkins et al.   PROTEOMICS

The G2019S mutation in LRRK2 imparts resiliency to kinase inhibition

(2018) Kaela Kelly et al.   EXPERIMENTAL NEUROLOGY

Nigrostriatal pathology with reduced astrocytes in LRRK2 S910/S935 phosphorylation deficient knockin mice

(2018) Ye Zhao et al.   NEUROBIOLOGY OF DISEASE

LRRK2 activation in idiopathic Parkinson’s disease

(2018) Roberto Di Maio et al.   Science Translational Medicine

Inhibition of LRRK2 or Casein Kinase 1 Results in LRRK2 Protein Destabilization

(2018) T. De Wit et al.   MOLECULAR NEUROBIOLOGY

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

PAK6 Phosphorylates 14-3-3γ to Regulate Steady State Phosphorylation of LRRK2

(2017) Laura Civiero et al.   Frontiers in Molecular Neuroscience

Elevated LRRK2 autophosphorylation in brain-derived and peripheral exosomes in LRRK2 mutation carriers

(2017) Shijie Wang et al.   Acta Neuropathologica Communications

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

(2017) Francesco Longo et al.   Acta Neuropathologica Communications

Cryo-EM analysis of homodimeric full-length LRRK2 and LRRK1 protein complexes

(2017) Kushal Sejwal et al.   Scientific Reports

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 Kinase Inhibition as a Therapeutic Strategy for Parkinson's Disease, Where Do We Stand?

(2016) Jean-Marc Taymans et al.   Current Neuropharmacology

LRRK2 autophosphorylation enhances its GTPase activity

(2016) Zhiyong Liu et al.   FASEB JOURNAL

LRRK2BAC transgenic rats develop progressive, L-DOPA-responsive motor impairment, and deficits in dopamine circuit function

(2016) Max Sloan 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

Parkinson-Related LRRK2 Mutation R1628P Enables Cdk5 Phosphorylation of LRRK2 and Upregulates Its Kinase Activity

(2016) Yang Shu et al.   PLoS One

Activation of FADD-Dependent Neuronal Death Pathways as a Predictor of Pathogenicity for LRRK2 Mutations

(2016) Katerina Melachroinou et al.   PLoS One

Structural model of the dimeric Parkinson’s protein LRRK2 reveals a compact architecture involving distant interdomain contacts

(2016) Giambattista Guaitoli et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1

(2016) Frederick C. Nucifora et al.   Nature Communications

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

(2016) G. Perera et al.   Scientific Reports

LRRK2 phosphorylation level correlates with abnormal motor behaviour in an experimental model of levodopa-induced dyskinesias

(2016) Jennifer Stanic et al.   Molecular Brain

Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation

(2016) E. Lobbestael et al.   Scientific Reports

LRRK2 dephosphorylation increases its ubiquitination

(2015) Jing Zhao et al.   BIOCHEMICAL JOURNAL

Pathogenic LRRK2 mutations, through increased kinase activity, produce enlarged lysosomes with reduced degradative capacity and increase ATP13A2 expression

(2015) Anastasia G. Henry 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

Multisystem Lewy body disease and the other parkinsonian disorders

(2015) J William Langston et al.   NATURE GENETICS

Increased oligomerization and phosphorylation of α-synuclein are associated with decreased activity of glucocerebrosidase and protein phosphatase 2A in aging monkey brains

(2015) Guangwei Liu et al.   NEUROBIOLOGY OF AGING

Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice

(2015) M. Yue et al.   NEUROBIOLOGY OF DISEASE

A visual review of the interactome of LRRK2: Using deep-curated molecular interaction data to represent biology

(2015) Pablo Porras et al.   PROTEOMICS

Effect of selective LRRK2 kinase inhibition on nonhuman primate lung

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

Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains

(2015) Min Chen et al.   Oncotarget

EvaluatingLRRK2Genetic Variants with Unclear Pathogenicity

(2015) Fathima Shaffra Refai et al.   Biomed Research International

Computational analysis of the LRRK2 interactome

(2015) Claudia Manzoni et al.   PeerJ

A Novel GTP-Binding Inhibitor, FX2149, Attenuates LRRK2 Toxicity in Parkinson’s Disease Models

(2015) Tianxia Li et al.   PLoS One

LRRK2, a puzzling protein: Insights into Parkinson's disease pathogenesis

(2014) A. Raquel Esteves et al.   EXPERIMENTAL NEUROLOGY

Unique Functional and Structural Properties of the LRRK2 Protein ATP-binding Pocket

(2014) Zhiyong Liu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

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

Differential LRRK2 expression in the cortex, striatum, and substantia nigra in transgenic and nontransgenic rodents

(2014) Andrew B. West et al.   JOURNAL OF COMPARATIVE NEUROLOGY

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

(2014) Lauran Reyniers et al.   JOURNAL OF NEUROCHEMISTRY

LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity

(2014) Loukia Parisiadou et al.   NATURE NEUROSCIENCE

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

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

Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice

(2014) Dayne A. Beccano-Kelly et al.   Frontiers in Cellular Neuroscience

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

(2014) Ruth Chia et al.   Nature Communications

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

Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism

(2014) Jean-Marc Taymans et al.   Frontiers in Genetics

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

(2013) Evy Lobbestael et al.   BIOCHEMICAL JOURNAL

Differential Effects of Familial Parkinson Mutations in LRRK2 Revealed by a Systematic Analysis of Autophosphorylation

(2013) Shogo Kamikawaji et al.   BIOCHEMISTRY

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

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

A Direct Interaction between Leucine-rich Repeat Kinase 2 and Specific β-Tubulin Isoforms Regulates Tubulin Acetylation

(2013) Bernard M. H. Law et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

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

Neuroprotective Function of 14-3-3 Proteins in Neurodegeneration

(2013) Tadayuki Shimada et al.   Biomed Research International

LRRK2 and vesicle trafficking

(2012) Giovanna Sanna et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

The GTPase function of LRRK2

(2012) Jean-Marc Taymans   BIOCHEMICAL SOCIETY TRANSACTIONS

Phosphorylation of LRRK2: from kinase to substrate

(2012) Evy Lobbestael et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Analysis of LRRK2 accessory repeat domains: prediction of repeat length, number and sites of Parkinson's disease mutations

(2012) Ryan D. Mills et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

MicroRNA-205 regulates the expression of Parkinson's disease-related leucine-rich repeat kinase 2 protein

(2012) Hyun Jin Cho et al.   HUMAN MOLECULAR GENETICS

Temporal Expression of Mutant LRRK2 in Adult Rats Impairs Dopamine Reuptake

(2012) Hongxia Zhou et al.   International Journal of Biological Sciences

Classic and New Animal Models of Parkinson's Disease

(2012) Javier Blesa et al.   JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY

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 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

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

Rac1 Protein Rescues Neurite Retraction Caused by G2019S Leucine-rich Repeat Kinase 2 (LRRK2)

(2011) Diane Chan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

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

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

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

Phenotype in parkinsonian and nonparkinsonian LRRK2 G2019S mutation carriers

(2011) C. Marras et al.   NEUROLOGY

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

LRRK2 Kinase Activity Is Dependent on LRRK2 GTP Binding Capacity but Independent of LRRK2 GTP Binding

(2011) Jean-Marc Taymans 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

Parkinson's disease-related LRRK2 G2019S mutation results from independent mutational events in humans

(2010) Suzanne Lesage et al.   HUMAN MOLECULAR GENETICS

Serine 129 Phosphorylation Reduces the Ability of α-Synuclein to Regulate Tyrosine Hydroxylase and Protein Phosphatase 2Ain Vitroandin Vivo

(2010) Haiyan Lou et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Reevaluation of Phosphorylation Sites in the Parkinson Disease-associated Leucine-rich Repeat Kinase 2

(2010) Xiaojie Li et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant

(2010) Veronique Daniëls et al.   JOURNAL OF NEUROCHEMISTRY

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

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

Novel pathogenic LRRK2 p.Asn1437His substitution in familial Parkinson's disease

(2010) Jan O. Aasly et al.   MOVEMENT DISORDERS

The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease

(2010) Mark R. Cookson   NATURE REVIEWS NEUROSCIENCE

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

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

The extended PP1 toolkit: designed to create specificity

(2010) Mathieu Bollen et al.   TRENDS IN BIOCHEMICAL SCIENCES

The Parkinson’s disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites

(2009) Elisa Greggio et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Identification of the Autophosphorylation Sites of LRRK2

(2009) Shogo Kamikawaji et al.   BIOCHEMISTRY

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

Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment

(2009) Christian L. Klein et al.   JOURNAL OF NEUROCHEMISTRY

Parkin Protects against LRRK2 G2019S Mutant-Induced Dopaminergic Neurodegeneration in Drosophila

(2009) C.-H. Ng et al.   JOURNAL OF NEUROSCIENCE

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

The WD40 Domain Is Required for LRRK2 Neurotoxicity

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

Comprehensive analysis ofLRRK2in publicly available Parkinson's disease cases and neurologically normal controls

(2008) Coro Paisán-Ruíz et al.   HUMAN MUTATION

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

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

(2008) Daniel G Healy et al.   LANCET 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