Journal Article

DZNE-2020-03756

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Interferon-γ induces leucine-rich repeat kinase LRRK2 via extracellular signal-regulated kinase ERK5 in macrophages.

Kuß, M. (First author)DZNE* ; Adamopoulou, E. ; Kahle, P. J. (Last author)DZNE*

2014
Wiley-Blackwell Oxford

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Please use a persistent id in citations: doi:10.1111/jnc.12668

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.

Keyword(s): Protein Serine-Threonine Kinases: biosynthesis (MeSH) ; Blotting, Western (MeSH) ; Cells, Cultured (MeSH) ; Cytokines: metabolism (MeSH) ; Enzyme Induction: drug effects (MeSH) ; Enzyme Inhibitors: pharmacology (MeSH) ; Humans (MeSH) ; Immunohistochemistry (MeSH) ; Interferon-gamma: antagonists & inhibitors (MeSH) ; Interferon-gamma: pharmacology (MeSH) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (MeSH) ; Macrophages: drug effects (MeSH) ; Macrophages: enzymology (MeSH) ; Mitogen-Activated Protein Kinase 7: antagonists & inhibitors (MeSH) ; Mitogen-Activated Protein Kinase 7: physiology (MeSH) ; Protein-Serine-Threonine Kinases: biosynthesis (MeSH) ; Real-Time Polymerase Chain Reaction (MeSH) ; Signal Transduction: drug effects (MeSH) ; Cytokines ; Enzyme Inhibitors ; Interferon-gamma ; LRRK2 protein, human ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Protein-Serine-Threonine Kinases ; Mitogen-Activated Protein Kinase 7

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Contributing Institute(s):

1. AG N.N. (AG N.N. 3)
2. Functional Neurogenetics (AG Kahle 2)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)
2. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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