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Glycogen Synthase Kinase 3β negatively regulates myogenic differentiation
Author(s) -
van der Velden Jos,
Langen Ramon,
Kelders Marco,
JanssenHeininger Yvonne,
Wouters Emiel,
Schols Annemie
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a392
Subject(s) - gsk 3 , transactivation , myod , myogenin , gsk3b , myocyte , c2c12 , glycogen synthase , myogenic regulatory factors , kinase , gene knockdown , transfection , chemistry , myogenesis , myf5 , microbiology and biotechnology , skeletal muscle , biology , transcription factor , endocrinology , phosphorylation , biochemistry , gene
Glycogen Synthase Kinase 3β (GSK‐3β) has been implicated in the negative regulation of both cardiac and skeletal muscle hypertrophy. Recently we showed that pharmacological inactivation of GSK‐3β is sufficient to stimulate myogenic differentiation. To further investigate the role of GSK‐3β in this process, GSK‐3β expression was suppressed in C2C12 myoblasts by RNA interference, which resulted in increased Muscle Creatine Kinase (MCK) activity after 3 days of differentiation. In addition, myogenic conversion of Mouse Embryonic Fibroblasts (MEF) by over‐expression of the muscle transcription factor MyoD resulted in enhanced transactivation of a co‐transfected Troponin‐I promoter‐reporter construct in GSK‐3β‐/‐ compared to WT MEFs. Furthermore, transient transfection of GSK‐3β‐/‐ MEFs with a GSK‐3β expression construct reduced Troponin‐I promoter transactivation, whereas co‐transfection of a kinase inactive variant (K85R) of GSK‐3β did not affect increased myogenic conversion of GSK‐3β‐/‐ MEFs. This implies that GSK‐3β kinase activity is required for its negative regulatory role in myogenic differentiation. Therefore inactivation of GSK‐3β can have a potential therapeutical role in prevention or treatment of muscle wasting. This abstract was sponsored by the Netherlands Asthma Foundation (320263).