Spence Heather J, Dhillon Amardeep S, James Marian, Winder Steven J
The Beatson Institute for Cancer Research, CRUK Beatson Laboratories, Switchback Road, Glasgow G61 1BD, UK.
EMBO Rep. 2004 May;5(5):484-9. doi: 10.1038/sj.embor.7400140. Epub 2004 Apr 8.
Dystroglycan is an important cell adhesion receptor linking the actin cytoskeleton, via utrophin and dystrophin, to laminin in the extracellular matrix. To identify adhesion-related signalling molecules associated with dystroglycan, we conducted a yeast two-hybrid screen and identified mitogen-activated protein (MAP) kinase kinase 2 (MEK2) as a beta-dystroglycan interactor. Pull-down experiments and localization studies substantiated a physiological link between beta-dystroglycan and MEK and localized MEK with dystroglycan in membrane ruffles. Moreover, we also identified active extracellular signal-regulated kinase (ERK), the downstream kinase from MEK, as another interacting partner for beta-dystroglycan and localized both active ERK and dystroglycan to focal adhesions in fibroblast cells. These studies suggest a role for dystroglycan as a multifunctional adaptor or scaffold capable of interacting with components of the ERK-MAP kinase cascade including MEK and ERK. These findings have important implications for our understanding of the role of dystroglycan in normal cellular processes and in disease states such as muscular dystrophy.
肌营养不良聚糖是一种重要的细胞黏附受体，它通过肌营养蛋白和抗肌萎缩蛋白将肌动蛋白细胞骨架与细胞外基质中的层粘连蛋白相连。为了鉴定与肌营养不良聚糖相关的黏附相关信号分子，我们进行了酵母双杂交筛选，并鉴定出丝裂原活化蛋白（MAP）激酶激酶2（MEK2）是β-肌营养不良聚糖的相互作用蛋白。下拉实验和定位研究证实了β-肌营养不良聚糖与MEK之间的生理联系，并将MEK与肌营养不良聚糖定位在膜皱褶中。此外，我们还鉴定出MEK的下游激酶——活性细胞外信号调节激酶（ERK）是β-肌营养不良聚糖的另一个相互作用伴侣，并将活性ERK和肌营养不良聚糖都定位在成纤维细胞的黏着斑中。这些研究表明，肌营养不良聚糖作为一种多功能衔接蛋白或支架，能够与ERK-MAP激酶级联反应的组分（包括MEK和ERK）相互作用。这些发现对于我们理解肌营养不良聚糖在正常细胞过程以及诸如肌肉萎缩症等疾病状态中的作用具有重要意义。
