Department of Pharmacology, Boston University School of Medicine, Boston, MA, USA.
Neurodegener Dis. 2010;7(1-3):68-75. doi: 10.1159/000285509. Epub 2010 Feb 18.
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.
越来越多的证据支持 LRRK2 功能与 MAP 激酶级联之间存在假定的联系。我们最近证明 LRRK2 与 MKK6、-3 和 -7 结合。先前的研究表明，支架蛋白在调节应激激酶复合物的亚细胞定位方面是必不可少的。c-jun NH2 末端激酶 (JNK)-相互作用蛋白 (JIP) 是一组支架蛋白，在调节 MAP 激酶信号级联中发挥重要作用。JIP1-3 已知可调节 JNK 途径的特异性和定位，而 JIP4 是 p38 途径的特异性支架蛋白。我们证明 LRRK2 与 JIP1-4 结合，并与总 JIP1、-3、-4、寡聚 JIP 和泛素化 JIP 的水平增加相关。这些结果与 LRRK2 在调节应激激酶级联中的假定作用一致。
