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Dystroglycan, a scaffold for the ERK–MAP kinase cascade
Author(s) -
Spence Heather J,
Dhillon Amardeep S,
James Marian,
Winder Steven J
Publication year - 2004
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400140
Subject(s) - dystroglycan , microbiology and biotechnology , mapk/erk pathway , focal adhesion , utrophin , laminin , mitogen activated protein kinase kinase , biology , map kinase kinase kinase , integrin , chemistry , protein kinase a , kinase , dystrophin , extracellular matrix , signal transduction , muscular dystrophy , biochemistry , cell , genetics
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 β‐dystroglycan interactor. Pull‐down experiments and localization studies substantiated a physiological link between β‐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 β‐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.