Dystroglycan, a scaffold for the ERK–MAP kinase cascade
| Autor: | Steven J. Winder, Amardeep S. Dhillon, Heather J. Spence, Marian James |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
musculoskeletal diseases
MAPK/ERK pathway congenital hereditary and neonatal diseases and abnormalities animal structures MAP Kinase Signaling System MAP Kinase Kinase 2 Scientific Report Biochemistry Dystroglycans Mice Laminin Two-Hybrid System Techniques Chlorocebus aethiops Utrophin Cell Adhesion Genetics Dystroglycan Animals Humans Extracellular Signal-Regulated MAP Kinases Molecular Biology Cells Cultured Cytoskeleton biology Fibroblasts musculoskeletal system Actin cytoskeleton Cell biology COS Cells biology.protein Pikachurin Dystrophin tissues HeLa Cells |
| Zdroj: | EMBO reports. 5:484-489 |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.1038/sj.embor.7400140 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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