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2020
7 Downloads (Pure)
Open Access
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Protein Kinases
Parkinson Disease
alpha-Synuclein
Missense Mutation
Protein Kinase Inhibitors
9 Downloads (Pure)

Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 Phosphorylation of Switch 2

Waschbüsch, D., Purlyte, E., Pal, P., McGrath, E., Alessi, D. R. & Khan, A. R., 3 Feb 2020, In : Structure.

Research output: Contribution to journalArticle

Open Access
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rab GTP-Binding Proteins
Phosphotransferases
Phosphorylation
Protein-Serine-Threonine Kinases
GTP Phosphohydrolases
2019
5 Citations (Scopus)
103 Downloads (Pure)

Crystal structure of the WD40 domain dimer of LRRK2

Zhang, P., Fan, Y., Ru, H., Wang, L., Magupalli, V. G., Taylor, S. S., Alessi, D. R. & Wu, H., 29 Jan 2019, In : Proceedings of the National Academy of Sciences of the United States of America. 116, 5, p. 1579-1584 6 p.

Research output: Contribution to journalArticle

Open Access
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Leucine
Phosphotransferases
Parkinson Disease
Dimerization
rab GTP-Binding Proteins
2 Citations (Scopus)
59 Downloads (Pure)

Design and Characterization of SGK3-PROTAC1, an Isoform Specific SGK3 Kinase PROTAC Degrader

Tovell, H., Testa, A., Zhou, H., Shpiro, N., Crafter, C., Ciulli, A. & Alessi, D., 20 Sep 2019, In : ACS Chemical Biology. 14, 9, p. 2024-2034 11 p.

Research output: Contribution to journalArticle

Open Access
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Phosphatidylinositol 3-Kinases
Protein Isoforms
Phosphotransferases
Cells
Degradation
1 Citation (Scopus)
47 Downloads (Pure)

Membrane association but not identity is required for LRRK2 activation and phosphorylation of Rab GTPases

Gomez, R. C., Wawro, P., Lis, P., Alessi, D. & Pfeffer, S. R., 2 Dec 2019, In : Journal of Cell Biology. 218, 12, p. 4157-4170 14 p.

Research output: Contribution to journalArticle

Open Access
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Guanine Nucleotide Dissociation Inhibitors
rab GTP-Binding Proteins
Guanosine Triphosphate
Phosphorylation
Membranes
37 Downloads (Pure)

Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44

Malik, N., Nirujogi, R. S., Peltier, J., Macartney, T., Wightman, M., Prescott, A., Gourlay, R., Trost, M., Alessi, D. & Karapetsas, A., 30 Oct 2019, In : Biochemical Journal. 476, 20, p. 3081-3107 27 p.

Research output: Contribution to journalArticle

Open Access
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Qa-SNARE Proteins
Phosphorylation
Phosphotransferases
SNARE Proteins
Substrates
1 Citation (Scopus)
27 Downloads (Pure)

PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins

Berndsen, K., Lis, P., Yeshaw, W. M., Wawro, P. S., Nirujogi, R., Wightman, M., Macartney, T., Dorward, M., Knebel, A., Tonelli, F., Pfeffer, S. R. & Alessi, D., 12 Nov 2019, In : eLife. 8, p. 1-37 37 p., e50416.

Research output: Contribution to journalArticle

Open Access
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Phosphoric Monoester Hydrolases
Phosphorylation
Phosphoprotein Phosphatases
Parkinson Disease
rab GTP-Binding Proteins
4 Citations (Scopus)
131 Downloads (Pure)

Rapid and reversible knockdown of endogenously tagged endosomal proteins via an optimized HaloPROTAC degrader

Tovell, H., Testa, A., Maniaci, C., Zhou, H., Prescott, A., Macartney, T., Ciulli, A. & Alessi, D., 17 May 2019, In : ACS Chemical Biology. 14, 5, p. 882-892 11 p.

Research output: Contribution to journalArticle

Open Access
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Degradation
Clustered Regularly Interspaced Short Palindromic Repeats
Proteins
Ubiquitination
Phosphorylation
2018
20 Citations (Scopus)
109 Downloads (Pure)

A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain

Dhekne, H. S., Yanatori, I., Gomez, R. C., Tonelli, F., Diez, F., Schüle, B., Steger, M., Alessi, D. R. & Pfeffer, S. R., 6 Nov 2018, In : eLife. 7, p. 1-26 26 p., e40202.

Research output: Contribution to journalArticle

Open Access
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Aptitude
Hedgehogs
Cilia
Neurons
Parkinson Disease
22 Citations (Scopus)
250 Downloads (Pure)

Development of phospho-specific Rab protein antibodies to monitor in vivo activity of the LRRK2 Parkinson’s disease kinase

Lis, P., Burel, S., Steger, M., Mann, M., Brown, F., Diez, F., Tonelli, F., Holton, J. L., Winglok Ho, P., Ho, S-L., Chou, M-Y., Polinski, N. K., Martinez, T. N., Davies, P. & Alessi, D. R., 2 Jan 2018, In : Biochemical Journal. 475, 1, p. 1-22 22 p.

Research output: Contribution to journalArticle

Open Access
File
Protein Kinases
Parkinson Disease
Phosphotransferases
Antibodies
Proteins
29 Downloads (Pure)

Discovery of potent and selective 5-azaindazole inhibitors of leucine-rich repeat kinase 2 (LRRK2): Part 1

Osborne, J., Birchall, K., Tsagris, D. J., Lewis, S. J., Smiljanic-Hurley, E., Taylor, D. L., Levy, A., Alessi, D. & McIver, E. G., 1 Dec 2018, In : Bioorganic & Medicinal Chemistry Letters.

Research output: Contribution to journalArticle

Open Access
File
Leucine
Phosphotransferases
Pharmaceutical Chemistry
Dopaminergic Neurons
Nervous System Diseases
1 Citation (Scopus)
147 Downloads (Pure)

Disruption of the with no lysine kinase-STE20-proline alanine-rich kinase pathway reduces the hypertension induced by angiotensin II

Graciela Cervantes-Perez, L., Castaneda-Bueno, M., Jimenez, J. V., Vazquez, N., Rojas-Vega, L., Alessi, D., Bobadilla, N. A. & Gamba, G., 1 Feb 2018, In : Journal of Hypertension. 36, 2, p. 361-367 7 p.

Research output: Contribution to journalArticle

Open Access
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Proline
Angiotensin II
Alanine
Lysine
Phosphotransferases
27 Citations (Scopus)
156 Downloads (Pure)

Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils

Fan, Y., Howden, A. J. M., Sarhan, A. R., Lis, P., Ito, G., Martinez, T. N., Brockmann, K., Gasser, T., Alessi, D. R. & Sammler, E., 2 Jan 2018, In : Biochemical Journal. 475, 1, p. 23-44 22 p.

Research output: Contribution to journalArticle

Open Access
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Phosphorylation
Leucine
Parkinson Disease
Neutrophils
Phosphotransferases
47 Citations (Scopus)
45 Downloads (Pure)

LRRK2 activation in idiopathic Parkinson's disease

Di Maio, R., Hoffman, E. K., Rocha, E. M., Keeney, M. T., Sanders, L. H., De Miranda, B. R., Zharikov, A., Van Laar, A., Stepan, A. F., Lanz, T. A., Kofler, J. K., Burton, E. A., Alessi, D. R., Hastings, T. G. & Timothy Greenamyre, J., 25 Jul 2018, In : Science Translational Medicine. 10, 451, p. 1-12 12 p., eaar5429.

Research output: Contribution to journalArticle

Open Access
File
Leucine
Parkinson Disease
Phosphotransferases
Ligation
Phosphorylation
34 Citations (Scopus)
135 Downloads (Pure)

LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages

Härtlova, A., Herbst, S., Peltier, J., Rodgers, A., Bilkei-Gorzo, O., Fearns, A., Dill, B. D., Lee, H., Flynn, R., Cowley, S. A., Davies, P., Lewis, P. A., Ganley, I. G., Martinez, J., Alessi, D. R., Reith, A. D., Trost, M. & Gutierrez, M. G., 15 Jun 2018, In : The EMBO Journal. 37, 12, p. 1-17 17 p., e98694.

Research output: Contribution to journalArticle

Open Access
File
Phagosomes
Macrophages
Mycobacterium tuberculosis
Leucine
Phosphotransferases
49 Citations (Scopus)
260 Downloads (Pure)

LRRK2 kinase in Parkinson's disease

Alessi, D. R. & Sammler, E., 6 Apr 2018, In : Science. 360, 6384, p. 36-37 2 p.

Research output: Contribution to journalComment/debate

Open Access
File
Leucine
Parkinson Disease
Phosphotransferases
Mutation
Clinical Trials, Phase I
8 Citations (Scopus)
212 Downloads (Pure)

Mechanism of activation of SGK3 by growth factors-via the Class 1 and Class 3 PI3Ks

Malik, N., Macartney, T., Hornberger, A., Anderson, K., Tovell, H., Prescott, A. R. & Alessi, D. R., 2 Jan 2018, In : Biochemical Journal. 475, 1, p. 117-135 19 p.

Research output: Contribution to journalArticle

Open Access
File
Phosphatidylinositol 3-Kinases
Intercellular Signaling Peptides and Proteins
Chemical activation
Phosphatidylinositols
Phosphotransferases
2 Citations (Scopus)
129 Downloads (Pure)

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

Zhao, Y., Keshiya, S., Atashrazm, F., Gao, J., Ittner, L. M., Alessi, D. R., Halliday, G. M., Fu, Y. & Dzamko, N., 1 Dec 2018, In : Neurobiology of Disease. 120, p. 76-87 12 p.

Research output: Contribution to journalArticle

Open Access
File
Leucine
Astrocytes
Parkinson Disease
Phosphotransferases
Phosphorylation
1 Citation (Scopus)
50 Downloads (Pure)

PP1 Phosphatase complexes: Undruggable No Longer

Vagnarelli, P. & Alessi, D. R., 23 Aug 2018, In : Cell. 174, 5, p. 1049-1051 3 p.

Research output: Contribution to journalArticle

Open Access
File
Phosphoprotein Phosphatases
Huntington Disease
Phosphoric Monoester Hydrolases
Phosphotransferases
Phosphorylation
6 Citations (Scopus)
94 Downloads (Pure)

Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinones as Inhibitors of Kinases and Bromodomains

Wang, J., Erazo, T., Ferguson, F. M., Buckley, D. L., Gomez, N., Muñoz-Guardiola, P., Diéguez-Martínez, N., Deng, X., Hao, M., Massefski, W., Fedorov, O., Offei-Addo, N. K., Park, P. M., Dai, L., DiBona, A., Becht, K., Kim, N. D., McKeown, M. R., Roberts, J. M., Zhang, J. & 8 others, Sim, T., Alessi, D. R., Bradner, J. E., Lizcano, J. M., Blacklow, S. C., Qi, J., Xu, X. & Gray, N. S., 21 Sep 2018, In : ACS Chemical Biology. 13, 9, p. 2438-2448 11 p.

Research output: Contribution to journalArticle

Open Access
File
Phosphotransferases
Polypharmacology
Mitogen-Activated Protein Kinase 7
Adenosine Triphosphate
Crystallography
27 Citations (Scopus)
107 Downloads (Pure)

The Parkinson's disease VPS35[D620N] mutation enhances LRRK2 mediated Rab protein phosphorylation in mouse and human

Mir, R., Tonelli, F., Lis, P., Macartney, T., Polinski, N. K., Martinez, T. N., Chou, M-Y., Howden, A., König, T., Hotzy, C., Milenkovic, I., Brücke, T., Zimprich, A., Sammler, E. & Alessi, D., 6 Jun 2018, In : Biochemical Journal. 475, 11, p. 1861-1883 19 p.

Research output: Contribution to journalArticle

Open Access
File
Phosphorylation
Parkinson Disease
Mutation
Proteins
Phosphotransferases
2017
4 Citations (Scopus)
133 Downloads (Pure)

B cell-intrinsic function of TAPP adaptors in controlling germinal center responses and autoantibody production in mice

Jayachandran, N., Landego, I., Hou, S., Alessi, D. R. & Marshall, A. J., 10 Feb 2017, In : European Journal of Immunology. 47, 2, p. 280-290 11 p.

Research output: Contribution to journalArticle

Open Access
File
Germinal Center
Autoantibodies
B-Lymphocytes
Proteins
Autoimmunity
49 Citations (Scopus)
148 Downloads (Pure)

Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

Maniaci, C., Hughes, S. J., Testa, A., Chen, W., Lamont, D. J., Rocha, S., Alessi, D. R., Romeo, R. & Ciulli, A., 10 Oct 2017, In : Nature Communications. 8, p. 1-14 14 p., 830.

Research output: Contribution to journalArticle

Open Access
File
Proteolysis
Ubiquitin-Protein Ligases
Hominidae
degradation
Degradation
21 Citations (Scopus)
126 Downloads (Pure)

Integrated single-cell genetic and transcriptional analysis suggests novel drivers of chronic lymphocytic leukemia

Wang, L., Fan, J., Francis, J. M., Georghiou, G., Hergert, S., Li, S., Gambe, R., Zhou, C. W., Yang, C., Xiao, S., Cin, P. D., Bowden, M., Kotliar, D., Shukla, S. A., Brown, J. R., Neuberg, D., Alessi, D. R., Zhang, C-Z., Kharchenko, P. V., Livak, K. J. & 1 others, Wu, C. J., 5 Jul 2017, In : Genome Research. 27, p. 1300-1311 11 p.

Research output: Contribution to journalArticle

Open Access
File
B-Cell Chronic Lymphocytic Leukemia
Genetic Heterogeneity
Neoplasms
RNA
Mutation
45 Citations (Scopus)
167 Downloads (Pure)

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

Purlyte, E., Dhekne, H. S., Sarhan, A. R., Gomez, R., Lis, P., Wightman, M., Martinez, T. N., Tonelli, F., Pfeffer, S. R. & Alessi, D. R., 15 Dec 2017, In : EMBO Journal. 36, 24, p. 3549-3681 18 p., e201798099.

Research output: Contribution to journalArticle

Open Access
File
Phosphorylation
Parkinson Disease
Phosphotransferases
Chemical activation
Biomarkers
4 Citations (Scopus)
104 Downloads (Pure)

Regulation of membrane ruffling by polarized STIM1 and ORAI1in cortactin-rich domains

M. López-Guerrero, A., Tomas-Martin, P., Pascual-Caro, C., Macartney, T., Rojas-Fernandez, A., Ball, G., Alessi, D. R., Pozo-Guisado, E. & Martin-Romero, F. J., 24 Mar 2017, In : Scientific Reports. 7, 15 p., 383.

Research output: Contribution to journalArticle

Open Access
File
Cortactin
Membranes
1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
Cytoskeleton
Cell Movement
11 Citations (Scopus)

Small-Molecule Inhibitors of LRRK2

Hatcher, J. M., Choi, H. G., Alessi, D. R. & Gray, N. S., 2017, Leucine-Rich Repeat Kinase 2 (LRRK2). Rideout, H. J. (ed.). Springer International Publishing, p. 241-264 24 p. (Advances in neurobiology; vol. 14).

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

Leucine
Phosphotransferases
Parkinson Disease
Mutation
Protein Kinases
70 Citations (Scopus)
212 Downloads (Pure)

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

Steger, M., Diez, F., Dhekne, H. S., Lis, P., Nirujogi, R. S., Karayel, O., Tonelli, F., Martinez, T. N., Lorentzen, E., Pfeffer, S. R., Alessi, D. R. & Mann, M., 10 Nov 2017, In : eLife. 6, p. 1-22 22 p., e31012.

Research output: Contribution to journalArticle

Open Access
File
rab GTP-Binding Proteins
Phosphorylation
Cilia
Proteomics
Pathology
60 Citations (Scopus)
361 Downloads (Pure)

USP7 small-molecule inhibitors interfere with ubiquitin binding

Kategaya, L., Di Lello, P., Rougé, L., Pastor, R., Clark, K. R., Drummond, J., Kleinheinz, T., Lin, E., Upton, J-P., Prakash, S., Heideker, J., McCleland, M., Ritorto, M. S., Alessi, D. R., Trost, M., Bainbridge, T. W., Kwok, M. C. M., Ma, T. P., Stiffler, Z., Brasher, B. & 24 others, Tang, Y., Jaishankar, P., Hearn, B. R., Renslo, A. R., Arkin, M. R., Cohen, F., Yu, K., Peale, F., Gnad, F., Chang, M. T., Klijn, C., Blackwood, E., Martin, S. E., Forrest, W. F., Ernst, J. A., Ndubaku, C., Wang, X., Beresini, M. H., Tsui, V., Schwerdtfeger, C., Blake, R. A., Murray, J., Maurer, T. & Wertz, I. E., 18 Oct 2017, In : Nature. 550, p. 534-538 5 p.

Research output: Contribution to journalLetter

Open Access
File
Ubiquitin-Specific Proteases
Ubiquitin
Magnetic Resonance Spectroscopy
Tumor Suppressor Protein p53
Proteins
20 Citations (Scopus)
122 Downloads (Pure)

Vomocytosis of live pathogens from macrophages is regulated by the atypical MAP kinase ERK5

Gilbert, A. S., Seoane, P. I., Sephton-Clark, P., Bojarczuk, A., Hotham, R., Giurisato, E., Sarhan, A. R., Hillen, A., Velde, G. V., Gray, N. S., Alessi, D. R., Cunningham, D. L., Tournier, C., Johnston, S. A. & May, R. C., 16 Aug 2017, In : Science Advances. 3, 8, p. 1-9 9 p., e1700898.

Research output: Contribution to journalArticle

Open Access
File
Mitogen-Activated Protein Kinase 7
Macrophages
Zebrafish
Vertebrates
Pharmacology
2016
13 Citations (Scopus)
116 Downloads (Pure)

Functional kinomics establishes a critical node of volume-sensitive cation-Cl- cotransporter regulation in the mammalian brain

Zhang, J., Gao, G., Begum, G., Wang, J., Khanna, A. R., Shmukler, B. E., Daubner, G. M., De Los Heros, P., Davies, P., Varghese, J., Bhuiyan, M. I. H., Duan, J., Zhang, J., Duran, D., Alper, S. L., Sun, D., Elledge, S. J., Alessi, D. R. & Kahle, K. T., 26 Oct 2016, In : Scientific Reports. 6, p. 1-19 19 p., 35986.

Research output: Contribution to journalArticle

Open Access
File
Cations
Phosphotransferases
Cell Size
Brain
Ion Transport
67 Citations (Scopus)
257 Downloads (Pure)

PDK1-SGK1 signaling sustains AKT-independent mTORC1 activation and confers resistance to PI3Kα inhibition

Castel, P., Ellis, H., Bago, R., Toska, E., Razavi, P., Carmona, F. J., kannan, S., Verma, C. S., Dickler, M., Chandarlapaty, S., Brogi, E., Alessi, D., Baselga, J. & Scaltriti, M., 8 Aug 2016, In : Cancer Cell. 30, 2, p. 229-242 14 p.

Research output: Contribution to journalArticle

Open Access
File
Phosphatidylinositol 3-Kinases
mechanistic target of rapamycin complex 1
Neoplasms
Cell Survival
Protein Isoforms
258 Citations (Scopus)
201 Downloads (Pure)

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

Steger, M., Tonelli, F., Ito, G., Davies, P., Trost, M., Vetter, M., Wachter, S., Lorentzen, E., Duddy, G., Wilson, S., Baptista, M. A. S., Fiske, B. K., Fell, M. J., Morrow, J. A., Reith, A. D., Alessi, D. R. & Mann, M., 29 Jan 2016, In : eLife. 5, p. 1-28 28 p., e12813.

Research output: Contribution to journalArticle

Open Access
File
rab GTP-Binding Proteins
Leucine
Parkinson Disease
Phosphotransferases
Guanine Nucleotide Dissociation Inhibitors
46 Citations (Scopus)
203 Downloads (Pure)

Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors

Ito, G., Katsemonova, K., Tonelli, F., Lis, P., Baptista, M., Shpiro, N., Duddy, G., Wilson, S., Wing-Lok Ho, P., Ho, S-L., Reith, A. D. & Alessi, D., 30 Aug 2016, In : Biochemical Journal. 473, 17, p. 2671-2685 15 p.

Research output: Contribution to journalArticle

Open Access
File
Phosphorylation
Leucine
Assays
Phosphotransferases
Fibroblasts
27 Citations (Scopus)
133 Downloads (Pure)

The hVPS34-SGK3 pathway counteracts inhibition of the PI3K-Akt to maintain mTORC1 and tumour growth

Bago, R., Eskelinen, E-L., Castel, P., Crafter, C., Bailey, F. P., Shpiro, N., Baselga, J., Cross, D., Eyers, P. & Alessi, D., 1 Sep 2016, In : EMBO Journal. 35, 17, p. 1902-1922 23 p.

Research output: Contribution to journalArticle

Open Access
File
Phosphatidylinositol 3-Kinases
Tumors
Growth
Chemical activation
Cells