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Interferon-? induces leucine-rich repeat kinase LRRK2 via extracellular signal-regulated kinase ERK5 in macrophages.
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J Neurochem 2014 Jan;
Authors: Martin Kuss, Eleni Adamopoulou, Philipp J Kahle
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-? (IFN-?) in monocytes, but the signaling pathway is not known. Here we show that IFN-? 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-? 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-? signal transduction pathway, pointing to new functions of ERK5 and LRRK2 in human macrophages. This article is protected by copyright. All rights reserved.
PMID: 24479685 [PubMed - as supplied by publisher]