Effect of contraction on mitogen-activated protein kinase signal transduction in skeletal muscle. Involvement Of the mitogen- and stress-activated protein kinase 1

J Biol Chem. 2000 Jan 14;275(2):1457-62. doi: 10.1074/jbc.275.2.1457.

Abstract

Growing evidence suggests that activation of mitogen-activated protein kinase (MAPK) signal transduction mediates changes in muscle gene expression in response to exercise. Nevertheless, little is known about upstream or downstream regulation of MAPK in response to muscle contraction. Here we show that ex vivo muscle contraction stimulates extracellular signal-regulated kinase 1 and 2 (ERK1/2), and p38(MAPK) phosphorylation. Phosphorylation of ERK1/2 or p38(MAPK) was unaffected by protein kinase C inhibition (GF109203X), suggesting that protein kinase C is not involved in mediating contraction-induced MAPK signaling. Contraction-stimulated phosphorylation of ERK1/2 and p38(MAPK) was completely inhibited by pretreatment with PD98059 (MAPK kinase inhibitor) and SB203580 (p38(MAPK) inhibitor), respectively. Muscle contraction also activated MAPK downstream targets p90 ribosomal S6 kinase (p90(Rsk)), MAPK-activated protein kinase 2 (MAPKAP-K2), and mitogen- and stress-activated protein kinase 1 (MSK1). Use of PD98059 or SB203580 revealed that stimulation of p90(Rsk) and MAPKAP-K2 most closely reflects ERK and p38(MAPK) stimulation, respectively. Stimulation of MSK1 in contracting skeletal muscle required the activation of both ERK and p38(MAPK). These data demonstrate that muscle contraction, separate from systemic influence, activates MAPK signaling. Furthermore, we are the first to show that contractile activity stimulates MAPKAP-K2 and MSK1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-O-Methylglucose / metabolism
  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Glycogen / metabolism
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Indoles / pharmacology
  • Insulin / pharmacology
  • Male
  • Maleimides / pharmacology
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / physiology*
  • Phosphopeptides / chemistry
  • Phosphorylation
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Signal Transduction / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Indoles
  • Insulin
  • Maleimides
  • Phosphopeptides
  • Pyridines
  • 3-O-Methylglucose
  • Glycogen
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • bisindolylmaleimide I
  • Tetradecanoylphorbol Acetate
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one