LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins

Neurodegener Dis. 2010;7(1-3):68-75. doi: 10.1159/000285509. Epub 2010 Feb 18.

Abstract

Increasing evidence supports a putative link between LRRK2 function and the MAP kinase cascades. We recently demonstrated that LRRK2 binds to MKK6, -3, and -7. Previous studies demonstrated that scaffold proteins are essential in the regulation of subcellular localization of stress kinase complexes. The c-jun NH2-terminal kinase (JNK)-interacting proteins (JIPs) are a group of scaffold proteins that play an important role in the regulation of MAP kinase signaling cascades. JIP1-3 are known to regulate the specificity and localization of the JNK pathway, while JIP4 is a specific scaffolding protein for the p38 pathway. We demonstrate that LRRK2 binds to JIP1-4, and is associated with increased levels of total JIP1, -3, -4, oligomeric JIP and ubiquitinated JIP. These results are consistent with a putative role of LRRK2 in regulating the stress kinase cascade.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Cell Line, Transformed
  • Humans
  • Immunoprecipitation / methods
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • MAP Kinase Signaling System / physiology*
  • Mutation / genetics
  • Oxidative Stress / genetics
  • Protein Binding / physiology
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Subcellular Fractions / metabolism
  • Transfection / methods

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein-Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases