title: Temporal changes in ERK phosphorylation are harmonious with 4E-BP1, but not p70S6K, during clenbuterol-induced hypertrophy in the rat gastrocnemius.
abstract: 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.
authors.affiliation: a Food Science Research Laboratories, R&D Division, Meiji Co., Ltd. 540 Naruda, Odawara, 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Sumi
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Higashi
authors.forename: Midori
authors.initials: M
authors.lastname: Natsume
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawahata
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakazato
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002976:Clenbuterol / Q000008:administration & dosage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006984:Hypertrophy / Q000139:chemically induced; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D002976:Clenbuterol
keywords: 4E-BP1; ERK; clenbuterol; eEF2; hypertrophie; hypertrophy; mTORC1; muscles squelettiques; p70S6K; rat; skeletal muscle