We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The kinase LRRK2 is a regulator of the transcription factor NFAT that modulates the severity of inflammatory bowel disease.
- Authors
Liu, Zhihua; Lee, Jinwoo; Krummey, Scott; Lu, Wei; Cai, Huaibin; Lenardo, Michael J
- Abstract
Leucine-rich repeat kinase 2 (LRRK2) has been identified by genome-wide association studies as being encoded by a major susceptibility gene for Crohn's disease. Here we found that LRRK2 deficiency conferred enhanced susceptibility to experimental colitis in mice. Mechanistic studies showed that LRRK2 was a potent negative regulator of the transcription factor NFAT and was a component of a complex that included the large noncoding RNA NRON (an NFAT repressor). Furthermore, the risk-associated allele encoding LRRK2 Met2397 identified by a genome-wide association study for Crohn's disease resulted in less LRRK2 protein post-translationally. Severe colitis in LRRK2-deficient mice was associated with enhanced nuclear localization of NFAT1. Thus, our study defines a new step in the control of NFAT activation that involves an immunoregulatory function of LRRK2 and has important implications for inflammatory bowel disease.
- Publication
Nature immunology, 2011, Vol 12, Issue 11, p1063
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.2113