Affinage

LRRK1

Leucine-rich repeat serine/threonine-protein kinase 1 · UniProt Q38SD2

Length
2015 aa
Mass
225.4 kDa
Annotated
2026-04-28
36 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LRRK1 is a GTP-regulated serine/threonine kinase that couples receptor signaling to intracellular membrane trafficking, cytoskeletal organization, and organelle dynamics. GTP binding to its Roc domain activates kinase activity (PMID:16243488), which is further stimulated allosterically by PKC-mediated phosphorylation of the CORB domain (Ser1064/Ser1074/Thr1075) (PMID:36040231) and held in check by dimer-dependent steric autoinhibition (PMID:37857821) and EGFR-mediated inhibitory phosphorylation at Tyr944 that is reversed by PTP1B at ER–endosome contact sites (PMID:22337768, PMID:36744428). LRRK1 is recruited to EGFR-bearing early endosomes via Grb2, where it phosphorylates Rab7A at Ser72 to drive dynein-dependent perinuclear endosome transport and ESCRT-mediated EGFR sorting (PMID:21245839, PMID:31085713), phosphorylates CLIP-170 at Thr1384 to recruit p150Glued to microtubule plus ends (PMID:25413345), phosphorylates CDK5RAP2 at Ser140 to promote γ-tubulin-dependent spindle orientation (PMID:26192437), phosphorylates NDEL1 at Ser155 downstream of PLK1 to drive dynein-2-mediated cilia disassembly (PMID:36254578), functions downstream of the ULK complex to initiate Parkin-mediated mitophagy via Rab7A Ser72 phosphorylation (PMID:36408770), and phosphorylates L-plastin at Ser5 to regulate osteoclast sealing zone formation (PMID:30136304). Loss-of-function mutations in LRRK1 cause osteosclerotic metaphyseal dysplasia (PMID:27055475).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2005 High

    Establishing that LRRK1 is a dual GTPase-kinase whose catalytic activity is positively regulated by GTP binding to the Roc domain answered the fundamental question of how this multi-domain protein is switched on.

    Evidence In vitro kinase and GTP-binding assays with Roc domain mutagenesis

    PMID:16243488

    Open questions at the time
    • Endogenous GEFs and GAPs controlling the GTP cycle were not identified
    • Physiological substrates were unknown
  2. 2011 High

    Demonstrating that LRRK1 is recruited to EGFR-containing early endosomes via Grb2 and regulates EGFR trafficking to multivesicular bodies established the primary cellular context for LRRK1 kinase function.

    Evidence Co-IP, live-cell imaging, siRNA knockdown, dominant-negative and kinase-dead mutants in mammalian cells

    PMID:21245839

    Open questions at the time
    • Direct substrates mediating endosome transport were not yet identified
    • Mechanism of kinase-activity dependence was unclear
  3. 2012 High

    Identifying EGFR-mediated Tyr944 phosphorylation as a negative feedback mechanism that attenuates LRRK1 kinase activity revealed a receptor-intrinsic brake on endosome motility and ILV sorting.

    Evidence In vitro kinase assay, Y944F mutagenesis, live-cell imaging of endosome dynamics

    PMID:22337768

    Open questions at the time
    • Phosphatase(s) reversing pY944 were unknown
    • Structural basis for inhibition was not determined
  4. 2014 High

    Identification of CLIP-170 Thr1384 as a direct LRRK1 substrate linked LRRK1 kinase activity to microtubule plus-end dynamics and dynein-dynactin recruitment, explaining how LRRK1 controls endosome motility at the cytoskeletal level.

    Evidence In vitro kinase assay, phospho-specific antibodies, Co-IP, live-cell imaging, mutagenesis

    PMID:25413345

    Open questions at the time
    • Whether CLIP-170 phosphorylation is required in non-endosomal contexts was not tested
    • Relationship to Rab-dependent motility mechanisms was unclear
  5. 2015 High

    Showing that PLK1/CDK1-activated LRRK1 phosphorylates CDK5RAP2 at Ser140 to promote γ-tubulin binding and astral microtubule nucleation expanded LRRK1 function beyond endosomal trafficking into mitotic spindle orientation control.

    Evidence In vitro kinase assay, mutagenesis, Co-IP, centrosome localization and spindle orientation phenotyping in knockdown cells

    PMID:26192437

    Open questions at the time
    • Whether LRRK1 phosphorylates additional centrosomal substrates was not addressed
    • Upstream signals specifying when PLK1 activates LRRK1 at centrosomes vs. cilia were not distinguished
  6. 2016 Medium

    Identification of LRRK1 loss-of-function mutations in patients with osteosclerotic metaphyseal dysplasia, together with demonstration that LRRK1 phosphorylates L-plastin at Ser5 to support osteoclast sealing zone formation, connected LRRK1 kinase activity to bone biology and human skeletal disease.

    Evidence Whole-exome sequencing, Lrrk1 KO osteoclasts, phosphoproteomics, phospho-specific antibodies, actin staining

    PMID:27055475 PMID:30136304

    Open questions at the time
    • Whether L-plastin is the sole relevant substrate in osteoclasts was not established
    • Patient-derived cell rescue experiments were not performed in the initial genetic study
  7. 2016 Medium

    Demonstrating that LRRK1 synergizes with CARMA1 to activate NF-κB downstream of the B-cell receptor revealed an immune signaling role for LRRK1 beyond membrane trafficking.

    Evidence Co-IP, Lrrk1 KO mouse B cells, NF-κB reporter assays, proliferation/survival assays

    PMID:27166870

    Open questions at the time
    • Whether LRRK1 kinase activity is required for NF-κB activation was not directly tested
    • Substrates in the BCR-NF-κB pathway were not identified
  8. 2019 High

    Identifying Rab7A Ser72 as a direct LRRK1 substrate at endosomal membranes, where phosphorylation promotes RILP binding and dynein-dynactin-dependent perinuclear transport, unified the endosomal trafficking function with a specific phosphorylation event.

    Evidence In vitro kinase assay, phospho-specific antibodies, Co-IP, live-cell imaging, LRRK1 knockdown

    PMID:31085713

    Open questions at the time
    • Rab7A phosphatase(s) counteracting this modification were not yet identified
    • Contribution of Rab7A Ser72 phosphorylation to ESCRT sorting was not directly tested
  9. 2021 High

    Systematic analysis in LRRK1 KO cells confirmed Rab7A as the primary Rab substrate of LRRK1 (not Rab8A/Rab10), identified PPM1H as its phosphatase, and showed that PD-equivalent mutations enhance LRRK1-mediated Rab7A phosphorylation, clarifying substrate selectivity and its potential disease relevance.

    Evidence MS-based phosphoproteomics in KO cells, in vitro kinase assays, phospho-specific antibodies, PKC activation, mutagenesis

    PMID:33459343

    Open questions at the time
    • Whether LRRK1 hyperactivating mutations cause neurodegenerative phenotypes in vivo was not tested
    • Structural basis for Rab7A selectivity over Rab8A/Rab10 was not determined
  10. 2022 High

    Demonstrating that PKC isoforms allosterically activate LRRK1 by phosphorylating the CORB domain (Ser1064/Ser1074/Thr1075) identified the principal upstream activation mechanism and distinguished it from the Rab29/VPS35 pathway that activates LRRK2.

    Evidence In vitro kinase assays with multiple PKC isoforms, phosphatase treatment, site-directed mutagenesis, PKC inhibitor studies

    PMID:36040231

    Open questions at the time
    • Which specific PKC isoform is physiologically dominant in each tissue context was not determined
    • Whether PKC-mediated activation is required for all LRRK1 functions or context-specific was not tested
  11. 2022 High

    Placing LRRK1 downstream of the ULK complex in Parkin-mediated mitophagy, where ATG13 recruits LRRK1 to mitochondria to phosphorylate Rab7A and initiate mitophagosome formation, expanded LRRK1 function to organelle quality control.

    Evidence LRRK1 KO, ATG13 KO, ectopic mitochondrial targeting rescue, phospho-Rab7 immunofluorescence, mitophagy assays

    PMID:36408770

    Open questions at the time
    • Whether LRRK1 has additional mitophagy substrates beyond Rab7A was not determined
    • Relationship between LRRK1-mediated mitophagy and neurodegeneration was not tested in vivo
  12. 2022 High

    Identifying NDEL1 Ser155 as a LRRK1 substrate downstream of PLK1 that promotes dynein-2-mediated cilia disassembly extended LRRK1 function to primary cilium dynamics and linked its kinase activity to intraflagellar transport.

    Evidence In vitro kinase assay, PLK1 inhibitor studies, Co-IP, phospho-specific antibodies, live-cell imaging of ciliary resorption

    PMID:36254578

    Open questions at the time
    • Whether LRRK1 loss causes ciliopathy-related phenotypes in vivo was not examined
    • Whether Rab7A phosphorylation also contributes to cilia disassembly was not tested
  13. 2023 High

    High-resolution cryo-EM structures revealed that LRRK1 autoinhibition is dimer-dependent (unlike LRRK2's monomer-intrinsic autoinhibition) and identified an additional autoinhibitory element, providing a structural framework for understanding how upstream activators relieve LRRK1 repression.

    Evidence Cryo-EM structures of monomeric and dimeric full-length LRRK1, comparison with LRRK2 structures

    PMID:37857821

    Open questions at the time
    • How PKC phosphorylation structurally relieves dimer-dependent autoinhibition was not modeled
    • Resolution was insufficient to visualize the active kinase conformation
  14. 2023 High

    Demonstrating that PTP1B at ER–endosome contact sites dephosphorylates LRRK1 pY944 to reactivate it, while LRRK1 reciprocally facilitates PTP1B-mediated EGFR dephosphorylation, established a bidirectional regulatory circuit at membrane contact sites.

    Evidence Co-IP, LRRK1/PTP1B knockdown, phospho-Y944 and phospho-EGFR Western blot, live-cell imaging of ER–endosome contacts

    PMID:36744428

    Open questions at the time
    • Whether other ER-resident phosphatases contribute was not tested
    • How LRRK1 spatially coordinates PTP1B access to EGFR at contact sites remains structurally undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dimer-dependent autoinhibition of LRRK1 is structurally relieved by PKC phosphorylation, what additional substrates exist in the mitophagy and NF-κB pathways, and whether LRRK1 hyperactivating mutations cause neurodegeneration in vivo remain unresolved.
  • Structural mechanism of PKC-induced activation not determined
  • In vivo consequences of gain-of-function mutations unknown
  • Full substrate repertoire incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0003924 GTPase activity 1
Localization
GO:0005768 endosome 5 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1 GO:0005929 cilium 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 1 R-HSA-1852241 Organelle biogenesis and maintenance 1 R-HSA-9612973 Autophagy 1
Partners
CDK5RAP2CLIP1EGFRGRB2LCP1NDEL1PTPN1RAB7A

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 LRRK1 is both a functional protein kinase and a GDP/GTP-binding protein; binding of GTP to the Roc domain stimulates LRRK1 kinase activity, suggesting LRRK1 cycles between a GTP-bound active and GDP-bound inactive state. In vitro kinase assay, GTP-binding assay, site-directed mutagenesis of Roc domain Cellular signalling High 16243488
2011 LRRK1 forms a complex with activated EGFR through an interaction with Grb2, is internalized with EGF into early endosomes, regulates EGFR transport from early to late endosomes in a kinase-activity-dependent manner, and serves as a scaffold facilitating EGFR interaction with the ESCRT-0 complex for sorting into multivesicular body inner vesicles. Co-immunoprecipitation, live-cell imaging, siRNA knockdown, dominant-negative and kinase-dead mutants Nature communications High 21245839
2012 EGFR phosphorylates LRRK1 at Tyr-944 upon EGF stimulation, reducing LRRK1 kinase activity; mutation Y944F abolishes this feedback, causing hyperactivation of LRRK1 kinase and enhanced motility of EGF-containing endosomes, with defective ILV formation in MVBs. In vitro kinase assay, site-directed mutagenesis (Y944F), live-cell imaging, endosomal trafficking assays Molecular biology of the cell High 22337768
2014 LRRK1 phosphorylates CLIP-170 at Thr1384 in its C-terminal zinc knuckle motif, promoting CLIP-170 association with dynein-dynactin complexes and accumulation of p150Glued at microtubule plus ends, thereby facilitating migration of EGFR-containing endosomes. In vitro kinase assay, phospho-specific antibodies, Co-IP, live-cell imaging, mutagenesis Journal of cell science High 25413345
2014 EGFR is a LRRK1-specific interactor (not LRRK2); 14-3-3 proteins are LRRK2-specific interactors. EGF induces translocation of LRRK1 (but not LRRK2) to endosomes, and phosphosite mapping shows LRRK1 lacks 14-3-3 consensus binding motifs. Protein microarray interaction screen, co-immunoprecipitation/mass spectrometry, phosphosite mapping, EGF stimulation assays Journal of neurochemistry High 24947832
2015 PLK1 phosphorylates LRRK1 at Ser1790, which is required for CDK1-mediated activation of LRRK1 at centrosomes. Activated LRRK1 then phosphorylates CDK5RAP2 at Ser140 in its γ-tubulin-binding motif, promoting CDK5RAP2 interaction with γ-tubulin and astral microtubule nucleation, thereby regulating mitotic spindle orientation. In vitro kinase assay, mutagenesis, Co-IP, centrosome localization assays, spindle orientation phenotyping in knockdown cells Nature cell biology High 26192437
2016 Loss-of-function mutations in LRRK1 cause osteosclerotic metaphyseal dysplasia (OSMD); in vitro studies using Lrrk1-deficient mouse osteoclasts demonstrated loss of LRRK1 kinase function underlies the bone phenotype. Whole exome sequencing, in vitro osteoclast functional assays with Lrrk1-deficient cells Journal of medical genetics Medium 27055475
2016 LRRK1 physically interacts with CARMA1 and synergizes with it to enhance NF-κB activation downstream of B-cell receptor signaling; Lrrk1-/- B cells show impaired BCR-mediated NF-κB activation and defects in proliferation, survival, and IgG3 class-switch recombination. Co-immunoprecipitation, Lrrk1 knockout mouse B cells, NF-κB reporter assays, proliferation and survival assays Scientific reports Medium 27166870
2017 Cryo-EM analysis revealed that full-length LRRK1 and LRRK2 form homodimers with two-fold symmetric orientations of protomers; the overall dimeric shapes of LRRK1 and LRRK2 are closely similar at 16–25 Å resolution, suggesting shared dimerization mechanisms. Cryo-electron microscopy and single particle analysis of purified full-length LRRK1 and LRRK2 Scientific reports Medium 28819229
2018 LRRK1 binds the Longin domain of VAMP7 and negatively regulates VAMP7-mediated lysosomal exocytosis; LRRK1 and VARP compete for VAMP7 binding in a tug-of-war that controls the peripheral pool of secretory lysosomes and cellular response to substrate rigidity. Co-immunoprecipitation, VAMP7 Longin domain binding assays, secretion assays in LRRK1-knockdown cells, atomic force microscopy iScience Medium 30240735
2018 LRRK1 phosphorylates L-plastin at Ser5 in osteoclasts; this phosphorylation is absent in Lrrk1-deficient osteoclasts and is required for proper actin assembly and sealing zone formation necessary for bone resorption. Metal affinity purification coupled LC/MS phosphoproteomics, phospho-specific antibodies, Lrrk1 KO osteoclasts, F-actin staining Journal of cellular biochemistry Medium 30136304
2019 GTP-bound Rab7A is phosphorylated by LRRK1 at Ser72 at the endosomal membrane; this phosphorylation promotes Rab7-RILP interaction, recruits the dynein-dynactin complex to Rab7-positive vesicles, and facilitates dynein-driven transport of EGFR-containing endosomes toward the perinuclear region. In vitro kinase assay with recombinant LRRK1 and Rab7A, co-immunoprecipitation, phospho-specific antibodies, live-cell imaging, LRRK1 knockdown Journal of cell science High 31085713
2020 A splice-site LRRK1 mutation causing exon 3 skipping (frameshift p.Ala34Profs*33) results in loss of LRRK1 kinase function in patient-derived osteoclasts, evidenced by strongly reduced phosphorylation of L-plastin at Ser5; patient osteoclasts are extremely large and can only superficially erode bone. cDNA sequencing, Western blot with phospho-L-plastin (Ser5) antibody, patient-derived monocyte-derived osteoclast functional assays Journal of bone and mineral research Medium 32119750
2021 In LRRK1 knockout cells, phosphorylation of Rab7A at Ser72 was most reduced; recombinant LRRK1 efficiently phosphorylated Rab7A at Ser72 but not Rab8A or Rab10. Phorbol ester stimulation markedly enhanced Rab7A Ser72 phosphorylation via LRRK1. LRRK2 regulators Rab29 and VPS35[D620N] do not influence LRRK1. PPM1H Rab phosphatase dephosphorylates Rab7A. LRRK1 mutations equivalent to LRRK2 Parkinson mutations (K746G and I1412T) enhance LRRK1-mediated Rab7A phosphorylation. Mass spectrometry in LRRK1 KO cells, in vitro kinase assay with recombinant LRRK1, novel phospho-specific antibody, mutagenesis, pharmacological inhibitor studies The Biochemical journal High 33459343
2010 LRRK1 and LRRK2 physically interact and form heterodimers, as demonstrated by co-immunoprecipitation. Co-immunoprecipitation Mechanisms of ageing and development Low 20144646
2014 FIH-1 (HIF1AN) binds LRRK1 and disrupts EGFR/LRRK1 complex formation, thereby increasing EGFR signaling and promoting keratinocyte migration via the MAPK/ERK pathway. Co-immunoprecipitation, in vitro scratch wound assay, FIH-1 null mouse wound healing, siRNA knockdown The American journal of pathology Medium 25455687
2022 PKC isoforms phosphorylate LRRK1 at a cluster of conserved residues (Ser1064, Ser1074, Thr1075) in the CORB GTPase domain, activating LRRK1 kinase activity; mutation of Thr1075 to Ala blocks PKC-mediated LRRK1 activation, and a triple Glu phosphomimetic mutation enhances LRRK1 kinase activity ~3-fold. PKC activates LRRK1 not through the kinase domain but allosterically through the CORB domain. In vitro kinase assay with recombinant LRRK1 and multiple PKC isoforms, phosphatase treatment, site-directed mutagenesis (Ala and Glu substitutions), PKC inhibitor studies in HEK293 cells The Biochemical journal High 36040231
2022 LRRK1 functions downstream of the ULK complex (ULK1/ULK2) in Parkin-mediated mitophagy; ULK complex component ATG13 recruits LRRK1 to mitochondria, where LRRK1 phosphorylates Rab7 at Ser72 to initiate mitophagosome formation. Ectopic targeting of active LRRK1 to mitochondria bypasses the requirement for ATG13. LRRK1 knockdown/knockout, ATG13 knockout, ectopic mitochondrial targeting constructs, phospho-Rab7 (Ser72) immunofluorescence, mitophagy assays Journal of cell science High 36408770
2022 PLK1 phosphorylates LRRK1 at the primary cilia base during ciliary resorption, activating LRRK1. Activated LRRK1 phosphorylates NDEL1 at Ser155, which promotes NDEL1 interaction with cytoplasmic dynein-2 intermediate chains, triggering cilia disassembly via dynein-2-driven retrograde intraflagellar transport. LRRK1 depletion (siRNA/KD), PLK1 inhibitor studies, in vitro kinase assay, Co-IP, phospho-specific antibodies, live-cell imaging of ciliary resorption Journal of cell science High 36254578
2023 Cryo-EM structures of monomeric and dimeric LRRK1 reveal that LRRK1 is sterically autoinhibited in a dimer-dependent manner (unlike LRRK2 which is autoinhibited as a monomer), and LRRK1 has an additional level of autoinhibition preventing kinase activation that is absent in LRRK2. Cryo-EM structure determination of full-length LRRK1 in monomeric and dimeric forms, structural comparison with LRRK2 Nature structural & molecular biology High 37857821
2023 LRRK1 facilitates EGFR dephosphorylation by the ER-localized phosphatase PTP1B at ER-endosome contact sites; LRRK1 is required for PTP1B-EGFR interaction after EGF stimulation. PTP1B in turn activates LRRK1 by dephosphorylating pY944, promoting EGFR-containing endosome transport to the perinuclear region and EGFR sorting into ILVs. Co-immunoprecipitation, LRRK1 knockdown, PTP1B knockdown, phospho-EGFR and phospho-LRRK1 (Y944) Western blot, live-cell imaging of ER-endosome contact sites Journal of cell science High 36744428

Source papers

Stage 0 corpus · 36 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Dynamic and redundant regulation of LRRK2 and LRRK1 expression. BMC neuroscience 120 18045479
2005 LRRK1 protein kinase activity is stimulated upon binding of GTP to its Roc domain. Cellular signalling 94 16243488
2007 Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1. Journal of neurochemistry 72 17394548
2011 Leucine-rich repeat kinase LRRK1 regulates endosomal trafficking of the EGF receptor. Nature communications 69 21245839
2013 Expression analysis of Lrrk1, Lrrk2 and Lrrk2 splice variants in mice. PloS one 66 23675505
2015 PLK1-dependent activation of LRRK1 regulates spindle orientation by phosphorylating CDK5RAP2. Nature cell biology 59 26192437
2014 Differential protein-protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways. Journal of neurochemistry 44 24947832
2021 Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms. The Biochemical journal 41 33459343
2019 LRRK1 phosphorylation of Rab7 at S72 links trafficking of EGFR-containing endosomes to its effector RILP. Journal of cell science 41 31085713
2016 Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity. Journal of medical genetics 38 27055475
2017 Cryo-EM analysis of homodimeric full-length LRRK2 and LRRK1 protein complexes. Scientific reports 37 28819229
2018 Biomechanical Control of Lysosomal Secretion Via the VAMP7 Hub: A Tug-of-War between VARP and LRRK1. iScience 28 30240735
2016 Identification of a novel LRRK1 mutation in a family with osteosclerotic metaphyseal dysplasia. Journal of human genetics 27 27829680
2012 EGFR-dependent phosphorylation of leucine-rich repeat kinase LRRK1 is important for proper endosomal trafficking of EGFR. Molecular biology of the cell 24 22337768
2014 LRRK1-phosphorylated CLIP-170 regulates EGFR trafficking by recruiting p150Glued to microtubule plus ends. Journal of cell science 23 25413345
2007 Variants in the LRRK1 gene and susceptibility to Parkinson's disease in Norway. Neuroscience letters 23 17324517
2013 Rare variants in LRRK1 and Parkinson's disease. Neurogenetics 22 24241507
2010 Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson disease. Mechanisms of ageing and development 20 20144646
2016 LRRK1 is critical in the regulation of B-cell responses and CARMA1-dependent NF-κB activation. Scientific reports 19 27166870
2020 Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 16 32119750
2020 LINC00511 exacerbated T-cell acute lymphoblastic leukemia via miR-195-5p/LRRK1 axis. Bioscience reports 14 32242897
2019 A novel homozygous LRRK1 stop gain mutation in a patient suspected with osteosclerotic metaphyseal dysplasia. Annals of human genetics 14 31571209
2023 LRRK1 functions as a scaffold for PTP1B-mediated EGFR sorting into ILVs at the ER-endosome contact site. Journal of cell science 11 36744428
2018 LRRK1 regulation of actin assembly in osteoclasts involves serine 5 phosphorylation of L-plastin. Journal of cellular biochemistry 11 30136304
2022 PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain. The Biochemical journal 10 36040231
2022 The ULK complex-LRRK1 axis regulates Parkin-mediated mitophagy via Rab7 Ser-72 phosphorylation. Journal of cell science 10 36408770
2014 FIH-1 disrupts an LRRK1/EGFR complex to positively regulate keratinocyte migration. The American journal of pathology 10 25455687
2023 Structure of LRRK1 and mechanisms of autoinhibition and activation. Nature structural & molecular biology 9 37857821
2021 Broadening the phenotype of LRRK1 mutations - Features of malignant osteopetrosis and optic nerve atrophy with intrafamilial variable expressivity. European journal of medical genetics 9 34798323
2018 Genetic Analysis of LRRK1 and LRRK2 Variants in Essential Tremor Patients. Genetic testing and molecular biomarkers 8 29812962
2022 LRRK1-mediated NDEL1 phosphorylation promotes cilia disassembly via dynein-2-driven retrograde intraflagellar transport. Journal of cell science 5 36254578
2019 A small molecular inhibitor of LRRK1 identified by homology modeling and virtual screening suppresses osteoclast function, but not osteoclast differentiation, in vitro. Aging 5 31113907
2023 Protein kinase C showcases allosteric control: activation of LRRK1. The Biochemical journal 1 36762701
2023 Osteosclerotic Metaphyseal Dysplasia Due to a Likely Pathogenic LRRK1 Variant as a Cause of Recurrent Long Bone Fractures. JBMR plus 1 37614307
2023 Case Report: Osteosclerotic metaphyseal dysplasia with optic nerve involvement and progressive osteonecrosis of the jaw due to a novel LRRK1 mutation. Frontiers in endocrinology 1 37920250
2021 Chemical IN04 Inhibits the Kinase Domain not the ROC Domain of LRRK1: Results from Homology Modeling and Molecular Docking. Medicinal chemistry (Shariqah (United Arab Emirates)) 0 32972350