LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins.
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.
Hsu
C H
CH
Department of Pharmacology, Boston University School of Medicine, Boston, MA, USA.
Chan
D
D
Wolozin
B
B
D000704:Analysis of Variance; D002461:Cell Line, Transformed; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection / Q000379:methods
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases