ERK2 is required for efficient terminal differentiation of skeletal myoblasts

Journal Article · Fri Jul 14 04:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

OSTI ID:20854355

Ju, Li ^[1]; Johnson, Sally E ^[1]

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1. Department of Animal Sciences, University of Florida, P.O. Box 110910, Gainesville, FL 32611 (United States)

Terminal differentiation of skeletal myoblasts involves alignment of the mononucleated cells, fusion into multinucleated syncitia, and transcription of muscle-specific genes. Myogenesis in vivo is regulated partially by IGF-I initiated signaling that results in activation of an intracellular phosphatidylinositol 3 kinase (PI3K) signaling cascade. Downstream signaling through the Raf/MEK/ERK axis, a pathway initiated by IGF-I, also is implicated in the regulation of muscle formation. The involvement of ERK1 and ERK2 during myogenesis was examined in C2C12 myoblasts. C2C12 myoblasts stably expressing a small interfering RNA (siRNA) directed against ERK1 or ERK2 were created. Both of the kinases were reduced to trace levels as measured by Western for total ERK and retained the capacity to become phosphorylated. C2C12siERK2 knockdown myoblasts failed to fuse into multinucleated myofibers. By contrast, cells expressing a scrambled siRNA or ERK1 siRNA fused into large multinucleated structures. The block to muscle formation did not involve continued cell cycle progression or apoptosis. C2C12siERK1 myoblasts expressed an increased amount of ERK2 protein and formed larger myofibers in response to IGF-I treatment. Interestingly, IGF-I treatment of C2C12 ERK2 knockdown myoblasts did not reinstate the myogenic program arguing that ERK2 is required for differentiation. These results provide evidence for ERK2 as a positive regulator of myogenesis and suggest that ERK1 is dispensable for myoblast proliferation and differentiation.

• OSTI ID: 20854355
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 345; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL CYCLE
CELL PROLIFERATION
GENE REGULATION
GENES
IN VIVO
MYOBLASTS
PHOSPHOTRANSFERASES
RNA
TRANSCRIPTION