LRRK2 enhances Nod1/2-mediated inflammatory cytokine production by promoting Rip2 phosphorylation.
10.1007/s13238-016-0326-x
- Author:
Ruiqing YAN
1
;
Zhihua LIU
2
Author Information
1. Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2. Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. zhihualiu@ibp.ac.cn.
- Publication Type:Journal Article
- Keywords:
Inflammation;
LRRK2;
NF-κB activation;
Nod2;
Rip2
- MeSH:
Animals;
Cytokines;
genetics;
immunology;
HEK293 Cells;
Humans;
Immunity, Innate;
genetics;
Inflammation;
genetics;
immunology;
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2;
genetics;
immunology;
Mice;
Mice, Knockout;
Nod1 Signaling Adaptor Protein;
genetics;
immunology;
Nod2 Signaling Adaptor Protein;
genetics;
immunology;
Phosphorylation;
genetics;
immunology;
Receptor-Interacting Protein Serine-Threonine Kinase 2;
genetics;
immunology;
Receptor-Interacting Protein Serine-Threonine Kinases;
genetics;
immunology;
Signal Transduction;
genetics;
immunology
- From:
Protein & Cell
2017;8(1):55-66
- CountryChina
- Language:English
-
Abstract:
The innate immune system is critical for clearing infection, and is tightly regulated to avert excessive tissue damage. Nod1/2-Rip2 signaling, which is essential for initiating the innate immune response to bacterial infection and ER stress, is subject to many regulatory mechanisms. In this study, we found that LRRK2, encoded by a gene implicated in Crohn's disease, leprosy and familial Parkinson's disease, modulates the strength of Nod1/2-Rip2 signaling by enhancing Rip2 phosphorylation. LRRK2 deficiency markedly reduces cytokine production in macrophages upon Nod2 activation by muramyl dipeptide (MDP), Nod1 activation by D-gamma-Glu-meso-diaminopimelic acid (iE-DAP) or ER stress. Our biochemical study shows that the presence of LRRK2 is necessary for optimal phosphorylation of Rip2 upon Nod2 activation. Therefore, this study reveals that LRRK2 is a new positive regulator of Rip2 and promotes inflammatory cytokine induction through the Nod1/2-Rip2 pathway.
