Biology of Neurodegeneration
LRRK2 and the Stress Response: Interaction with MKKs and JNK-Interacting ProteinsHsu C.H.a · Chan D.a · Wolozin B.a, b
Departments of aPharmacology and bNeurology, Boston University School of Medicine, Boston, Mass., USA
Departments of Pharmacology and Neurology, Boston University School of Medicine
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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.
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