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G2385R and I2020T Mutations Increase LRRK2 GTPase Activity
Joint Authors
Seo, Hyemyung
Son, Ilhong
Seol, Wongi
Ho, Dong Hwan
Jang, Jihoon
Joe, Eun-hye
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-05-25
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
The LRRK2 mutation is a major causal mutation in familial Parkinson’s disease.
Although LRRK2 contains functional GTPase and kinase domains and their activities are altered by pathogenic mutations, most studies focused on LRRK2 kinase activity because the most prevalent mutant, G2019S, enhances kinase activity.
However, the G2019S mutation is extremely rare in the Asian population.
Instead, the G2385R mutation was reported as a major risk factor in the Asian population.
Similar to other LRRK2 studies, G2385R studies have also focused on kinase activity.
Here, we investigated GTPase activities of G2385R with other LRRK2 mutants, such as G2019S, R1441C, and I2020T, as well as wild type (WT).
Our results suggest that both I2020T and G2385R contain GTPase activities stronger than that of WT.
A kinase assay using the commercial recombinant proteins showed that I2020T harbored stronger activity, whereas G2385R had weaker activity than that of WT, as reported previously.
This is the first report of LRRK2 I2020T and G2385R GTPase activities and shows that most of the LRRK2 mutations that are pathogenic or a risk factor altered either kinase or GTPase activity, suggesting that their physiological consequences are caused by altered enzyme activities.
American Psychological Association (APA)
Ho, Dong Hwan& Jang, Jihoon& Joe, Eun-hye& Son, Ilhong& Seo, Hyemyung& Seol, Wongi. 2016. G2385R and I2020T Mutations Increase LRRK2 GTPase Activity. BioMed Research International،Vol. 2016, no. 2016, pp.1-8.
https://search.emarefa.net/detail/BIM-1098883
Modern Language Association (MLA)
Ho, Dong Hwan…[et al.]. G2385R and I2020T Mutations Increase LRRK2 GTPase Activity. BioMed Research International No. 2016 (2016), pp.1-8.
https://search.emarefa.net/detail/BIM-1098883
American Medical Association (AMA)
Ho, Dong Hwan& Jang, Jihoon& Joe, Eun-hye& Son, Ilhong& Seo, Hyemyung& Seol, Wongi. G2385R and I2020T Mutations Increase LRRK2 GTPase Activity. BioMed Research International. 2016. Vol. 2016, no. 2016, pp.1-8.
https://search.emarefa.net/detail/BIM-1098883
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1098883