Related Experiment Video

Updated: Jun 9, 2026

Assaying the Kinase Activity of LRRK2 in vitro
06:09

Assaying the Kinase Activity of LRRK2 in vitro

Published on: January 18, 2012

14-3-3 proteins are promising LRRK2 interactors

Iakov N Rudenko1, Mark R Cookson

  • 1Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20982-3707, USA.

The Biochemical Journal
|August 28, 2010
PubMed

Insights

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause familial Parkinson's disease (PD). Researchers found LRRK2 interacts with 14-3-3 proteins, potentially stabilizing LRRK2 and offering new therapeutic avenues for PD.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic cause of familial Parkinson's disease (PD).
  • LRRK2 contains catalytic domains (GTPase, kinase) and poorly understood protein-protein interaction domains.
  • 14-3-3 proteins are regulatory molecules that bind phosphorylated signaling pathway components.

Purpose of the Study:

  • To investigate the interaction between the N-terminal region of LRRK2 and 14-3-3 proteins.
  • To identify specific residues in LRRK2 responsible for 14-3-3 binding.
  • To understand the functional implications of this interaction on LRRK2 structure and cellular distribution.

Main Methods:

  • Combination of biochemical techniques.
  • Identification of specific serine residues (Ser910 and Ser935) crucial for 14-3-3 binding.
  • Correlation of 14-3-3 binding with intracellular LRRK2 distribution patterns.

Main Results:

  • Identified Ser910 and Ser935 as critical for LRRK2 binding to 14-3-3 proteins.
  • Demonstrated that 14-3-3 binding can prevent dephosphorylation of Ser910/Ser935.
  • Observed that 14-3-3 interaction may stabilize LRRK2 structure, potentially through influencing dimerization.
  • Found a correlation between 14-3-3 binding and the intracellular localization of LRRK2.

Conclusions:

  • The interaction between LRRK2 and 14-3-3 proteins represents a significant regulatory mechanism for LRRK2.
  • This interaction may stabilize LRRK2 structure and influence its cellular function.
  • Understanding this mechanism could lead to novel therapeutic strategies for 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

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation12:49

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation

Published on: March 21, 2020

Related Concept Videos

Protein-protein Interfaces02:04

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
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 rapamycin-insensitive companion...
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,...
Protein Networks02:26

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.