Dystroglycan, a scaffold for the ERK-MAP kinase cascade.
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.
Spence
Heather J
HJ
The Beatson Institute for Cancer Research, CRUK Beatson Laboratories, Switchback Road, Glasgow G61 1BD, UK.
Dhillon
Amardeep S
AS
James
Marian
M
Winder
Steven J
SJ
D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D048370:MAP Kinase Kinase 2 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D020798:Two-Hybrid System Techniques
D049030:Dystroglycans; D048049:Extracellular Signal-Regulated MAP Kinases; D048370:MAP Kinase Kinase 2