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@ARTICLE{Ku:137434,
author = {Kuß, Martin and Adamopoulou, Eleni and Kahle, Philipp J},
title = {{I}nterferon-γ induces leucine-rich repeat kinase {LRRK}2
via extracellular signal-regulated kinase {ERK}5 in
macrophages.},
journal = {Journal of neurochemistry},
volume = {129},
number = {6},
issn = {0022-3042},
address = {Oxford},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2020-03756},
pages = {980-987},
year = {2014},
abstract = {The gene encoding leucine-rich repeat kinase 2 (LRRK2)
comprises a major risk factor for Parkinson's disease.
Recently, it has emerged that LRRK2 plays important roles in
the immune system. LRRK2 is induced by interferon-γ
(IFN-γ) in monocytes, but the signaling pathway is not
known. Here, we show that IFN-γ-mediated induction of LRRK2
was suppressed by pharmacological inhibition and RNA
interference of the extracellular signal-regulated kinase 5
(ERK5). This was confirmed by LRRK2 immunostaining, which
also revealed that the morphological responses to IFN-γ
were suppressed by ERK5 inhibitor treatment. Both human
acute monocytic leukemia THP-1 cells and human peripheral
blood monocytes stimulated the ERK5-LRRK2 pathway after
differentiation into macrophages. Thus, LRRK2 is induced via
a novel, ERK5-dependent IFN-γ signal transduction pathway,
pointing to new functions of ERK5 and LRRK2 in human
macrophages. Leucine-rich repeat kinase 2 (LRRK2) is a major
risk factor for the development of Parkinson's disease (PD).
However, the role of LRRK2 in the affected neurons remains
enigmatic. Recently, LRRK2 has been reported to be strongly
expressed in the immune system. Here, we demonstrate that
LRRK2 is induced by Interferon gamma via extracellular
signal-regulated kinase 5 (ERK5) in macrophages, thus
providing new insights in LRRK2 and ERK5 biology.},
keywords = {Protein Serine-Threonine Kinases: biosynthesis / Blotting,
Western / Cells, Cultured / Cytokines: metabolism / Enzyme
Induction: drug effects / Enzyme Inhibitors: pharmacology /
Humans / Immunohistochemistry / Interferon-gamma:
antagonists $\&$ inhibitors / Interferon-gamma: pharmacology
/ Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 /
Macrophages: drug effects / Macrophages: enzymology /
Mitogen-Activated Protein Kinase 7: antagonists $\&$
inhibitors / Mitogen-Activated Protein Kinase 7: physiology
/ Protein-Serine-Threonine Kinases: biosynthesis / Real-Time
Polymerase Chain Reaction / Signal Transduction: drug
effects / Cytokines (NLM Chemicals) / Enzyme Inhibitors (NLM
Chemicals) / Interferon-gamma (NLM Chemicals) / LRRK2
protein, human (NLM Chemicals) / Leucine-Rich Repeat
Serine-Threonine Protein Kinase-2 (NLM Chemicals) /
Protein-Serine-Threonine Kinases (NLM Chemicals) /
Mitogen-Activated Protein Kinase 7 (NLM Chemicals)},
cin = {AG N.N. 3 / AG Kahle 2},
ddc = {610},
cid = {I:(DE-2719)1240015 / I:(DE-2719)1210000-4},
pnm = {344 - Clinical and Health Care Research (POF3-344) / 345 -
Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24479685},
doi = {10.1111/jnc.12668},
url = {https://pub.dzne.de/record/137434},
}