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Updated: Feb 11, 2026

Assaying the Kinase Activity of LRRK2 in vitro
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Assaying the Kinase Activity of LRRK2 in vitro

Published on: January 18, 2012

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Detection of endogenous S1292 LRRK2 autophosphorylation in mouse tissue as a readout for kinase activity

Jillian H Kluss1, Melissa M Conti1, Alice Kaganovich1

  • 11Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD USA.

NPJ Parkinson'S Disease
|May 1, 2018
PubMed

Insights

Researchers developed a new method to detect LRRK2 autophosphorylation in vivo. This finding offers a novel way to monitor LRRK2 kinase activity for Parkinson's disease therapeutics.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Mutations in Leucine-rich repeat kinase 2 (LRRK2) are linked to Parkinson's disease, often by enhancing its kinase activity.
  • Targeting LRRK2 kinase activity presents a promising therapeutic strategy for Parkinson's disease.
  • Current biomarkers for LRRK2 kinase activity include phosphorylation at S935 and its Rab GTPase substrates, but in vivo detection of autophosphorylation is limited.

Purpose of the Study:

  • To develop a method for detecting endogenous Leucine-rich repeat kinase 2 (LRRK2) autophosphorylation in vivo.
  • To identify a reliable physiological readout for monitoring LRRK2 kinase activity in vivo.

Main Methods:

  • Developed a novel fractionation-based enrichment method.
  • Applied the method to detect endogenous autophosphorylation at S1292 of LRRK2 in mouse tissues.

Main Results:

  • Successfully detected endogenous S1292 LRRK2 autophosphorylation in mouse tissues.
  • Established S1292 autophosphorylation as a potential physiological readout for LRRK2 kinase activity.

Conclusions:

  • The developed method enables detection of endogenous LRRK2 autophosphorylation in vivo.
  • S1292 autophosphorylation is a viable candidate biomarker for monitoring LRRK2 kinase activity in Parkinson's disease research.

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