The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2

Panagiotis S Athanasopoulos; Rolf Heumann; Arjan Kortholt

doi:10.1515/hsz-2017-0332

The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2

Panagiotis S Athanasopoulos
, Rolf Heumann
, Arjan Kortholt^*

^*Corresponding author for this work

Cell Biochemistry

Research output: Contribution to journal › Article › Academic › peer-review

7 Citations (Scopus)

373 Downloads (Pure)

Abstract

Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson's Disease (PD). LRRK2 is a large protein with two enzymatic domains, a GTPase and a kinase domain. A cluster of (auto)-phosphorylation sites within the N-terminus of LRRK2 have been shown to be crucial for the localization of LRRK2 and is important for PD pathogenesis. In addition, phosphorylation of sites within the G-domain of the protein affect GTPase activity. Here we discuss the role of these (auto)-phosphorylation sites of LRRK2 and their regulation by phosphatases and upstream kinases.

Original language	English
Pages (from-to)	643-647
Number of pages	5
Journal	Biological Chemistry
Volume	399
Issue number	7
Early online date	12-Mar-2018
DOIs	https://doi.org/10.1515/hsz-2017-0332
Publication status	Published - Jul-2018
Event	Conference on Molecular Basis of Life - Bochum, Germany Duration: 1-Sept-2017 → …

Keywords

GTPase
kinase
neuronal degeneration
Parkinson's disease
phosphatases
DISEASE-ASSOCIATED MUTATIONS
SYNAPTIC VESICLE TRAFFICKING
REPEAT KINASE 2
PARKINSONS-DISEASE
GTP-BINDING
CYTOPLASMIC LOCALIZATION
PHOSPHORYLATION
PENETRANCE
PHENOTYPE
PROTEINS

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@article{6482c1997fd545c19c988fb4b643e7de,

title = "The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2",

abstract = "Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson's Disease (PD). LRRK2 is a large protein with two enzymatic domains, a GTPase and a kinase domain. A cluster of (auto)-phosphorylation sites within the N-terminus of LRRK2 have been shown to be crucial for the localization of LRRK2 and is important for PD pathogenesis. In addition, phosphorylation of sites within the G-domain of the protein affect GTPase activity. Here we discuss the role of these (auto)-phosphorylation sites of LRRK2 and their regulation by phosphatases and upstream kinases.",

keywords = "GTPase, kinase, neuronal degeneration, Parkinson's disease, phosphatases, DISEASE-ASSOCIATED MUTATIONS, SYNAPTIC VESICLE TRAFFICKING, REPEAT KINASE 2, PARKINSONS-DISEASE, GTP-BINDING, CYTOPLASMIC LOCALIZATION, PHOSPHORYLATION, PENETRANCE, PHENOTYPE, PROTEINS",

author = "Athanasopoulos, \{Panagiotis S\} and Rolf Heumann and Arjan Kortholt",

year = "2018",

month = jul,

doi = "10.1515/hsz-2017-0332",

language = "English",

volume = "399",

pages = "643--647",

journal = "Biological Chemistry",

issn = "1437-4315",

publisher = "Walter de Gruyter GmbH",

number = "7",

note = "Conference on Molecular Basis of Life ; Conference date: 01-09-2017",

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TY - JOUR

T1 - The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2

AU - Athanasopoulos, Panagiotis S

AU - Heumann, Rolf

AU - Kortholt, Arjan

PY - 2018/7

Y1 - 2018/7

N2 - Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson's Disease (PD). LRRK2 is a large protein with two enzymatic domains, a GTPase and a kinase domain. A cluster of (auto)-phosphorylation sites within the N-terminus of LRRK2 have been shown to be crucial for the localization of LRRK2 and is important for PD pathogenesis. In addition, phosphorylation of sites within the G-domain of the protein affect GTPase activity. Here we discuss the role of these (auto)-phosphorylation sites of LRRK2 and their regulation by phosphatases and upstream kinases.

AB - Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson's Disease (PD). LRRK2 is a large protein with two enzymatic domains, a GTPase and a kinase domain. A cluster of (auto)-phosphorylation sites within the N-terminus of LRRK2 have been shown to be crucial for the localization of LRRK2 and is important for PD pathogenesis. In addition, phosphorylation of sites within the G-domain of the protein affect GTPase activity. Here we discuss the role of these (auto)-phosphorylation sites of LRRK2 and their regulation by phosphatases and upstream kinases.

KW - GTPase

KW - kinase

KW - neuronal degeneration

KW - Parkinson's disease

KW - phosphatases

KW - DISEASE-ASSOCIATED MUTATIONS

KW - SYNAPTIC VESICLE TRAFFICKING

KW - REPEAT KINASE 2

KW - PARKINSONS-DISEASE

KW - GTP-BINDING

KW - CYTOPLASMIC LOCALIZATION

KW - PHOSPHORYLATION

KW - PENETRANCE

KW - PHENOTYPE

KW - PROTEINS

U2 - 10.1515/hsz-2017-0332

DO - 10.1515/hsz-2017-0332

M3 - Article

C2 - 29537215

SN - 1437-4315

VL - 399

SP - 643

EP - 647

JO - Biological Chemistry

JF - Biological Chemistry

IS - 7

T2 - Conference on Molecular Basis of Life

Y2 - 1 September 2017

ER -

The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2

Abstract

Keywords

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