Extracellular signal-regulated kinase (ERK) is required for
clenbuterol (CB)-dependent fast-type myofibril enlargement; however, its contribution to translation control is unclear. ERK mediates translational regulation through
mammalian target of rapamycin complex 1 (
mTORC1) activation and (or) mTORC1-independent pathways. In this study, we aimed to investigate the role of ERK in translational control during CB-induced muscular
hypertrophy by measuring time-dependent changes in the phosphorylation statuses of ERK, p70 ribosomal
S6 kinase (
p70S6K; an
indicator of
mTORC1 activity), 4E-binding
protein 1 (4E-BP1), eukaryotic
elongation factor 2 (eEF2), and other related signaling molecules in rat gastrocnemius muscles. Five-day administration of CB induced phenotypes associated with muscular
hypertrophy (significant increases in wet weight and isometric ankle flexion torque in the gastrocnemius muscle), but was not accompanied by elevated ERK or
p70S6K phosphorylation. One-day administration of CB caused significant increases in the phosphorylation of ERK,
p70S6K, and 4E-BP1. In contrast, 3-day administration of CB caused significant increases in the phosphorylation of ERK and 4E-BP1, but not
p70S6K. In addition, positive correlations were observed between ERK and 4E-BP1 on days 1 and 3, whereas a correlation between ERK and
p70S6K was only observed on day 1. eEF2 phosphorylation was unchanged on both days 1 and 3. These findings suggest that ERK accelerates the initiation of translation, but does not support the involvement of ERK in translational elongation. Furthermore, ERK may play a major role in promoting translational initiation by mediating the phosphorylation of 4E-BP1, and may contribute to the initial activation of
mTORC1 during CB administration.