Related Experiment Video

Updated: Apr 19, 2026

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
08:55

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

16.4K

Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with

Ruth Chia1, Sara Haddock1, Alexandra Beilina1

  • 1Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, Maryland 20892-3707, USA.

Nature Communications
|December 16, 2014
PubMed

Insights

Researchers identified casein kinase 1α (CK1α) as the kinase responsible for LRRK2 phosphorylation, a key factor in Parkinson's disease. This finding sheds light on LRRK2 regulation and its role in cellular pathways potentially linked to Parkinson's pathogenesis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • The leucine-rich repeat kinase 2 (LRRK2) gene is implicated in Parkinson's disease pathogenesis.
  • LRRK2 protein possesses GTPase and kinase activities and is regulated by phosphorylation.
  • The specific kinases responsible for LRRK2 phosphorylation remain unidentified.

Purpose of the Study:

  • To identify the kinase(s) responsible for LRRK2 phosphorylation.
  • To investigate the functional consequences of LRRK2 phosphorylation by CK1α.
  • To elucidate the role of LRRK2 phosphorylation in cellular pathways relevant to Parkinson's disease.

Main Methods:

  • Unbiased siRNA kinome screening to identify kinases.
  • Validation of identified kinase using biochemical assays.
  • Analysis of LRRK2 protein interactions and localization.

Main Results:

  • Casein kinase 1α (CK1α) was identified as the primary kinase phosphorylating LRRK2.
  • CK1α-mediated phosphorylation regulates LRRK2 recruitment to Golgi-derived vesicles.
  • Phosphorylation affects LRRK2 interactions with ARHGEF7, influencing cellular pathways.

Conclusions:

  • CK1α is a key regulator of LRRK2 phosphorylation.
  • LRRK2 phosphorylation by CK1α modulates its interactions and localization.
  • These findings provide insights into LRRK2 function in Golgi maintenance and Parkinson's disease.

More Related Videos

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate11:31

Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Published on: September 18, 2013

10.6K
Assaying the Kinase Activity of LRRK2 in vitro06:09

Assaying the Kinase Activity of LRRK2 in vitro

Published on: January 18, 2012

23.1K

Related Concept Videos

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
19.7K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.5K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
16.2K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
7.2K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
8.4K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.8K