Marathon running increases ERK1/2 and p38 MAP kinase signalling to downstream targets in human skeletal muscle

J Physiol. 2001 Oct 1;536(Pt 1):273-82. doi: 10.1111/j.1469-7793.2001.00273.x.


1. We tested the hypothesis that long-distance running activates parallel mitogen-activated protein kinase (MAPK) cascades that involve extracellular signal regulated kinase 1 and 2 (ERK1/2) and p38 MAPK and their downstream substrates. 2. Eleven men completed a 42.2 km marathon (mean race time 4 h 1 min; range 2 h 56 min to 4 h 33 min). Vastus lateralis muscle biopsies were obtained before and after the race. Glycogen content was measured spectrophotometrically. ERK1/2 and p38 MAPK phosphorylation was determined by immunoblot analysis using phosphospecific antibodies. Activation of the downstream targets of ERK1/2 and p38 MAPK, MAPK-activated protein kinase-1 (MAPKAP-K1; also called p90 ribosomal S6 kinase, p90rsk), MAPK-activated protein kinase-2 (MAPKAP-K2), mitogen- and stress-activated kinase 1 (MSK1) and mitogen- and stress-activated kinase 2 (MSK2) was determined using immune complex assays. 3. Muscle glycogen content was reduced by 40 +/- 6 % after the marathon. ERK1/2 phosphorylation increased 7.8-fold and p38 MAPK phosphorylation increased 4.4-fold post-exercise. Prolonged running did not alter ERK1/2 and p38 MAPK protein expression. The activity of p90rsk, a downstream target of ERK1/2, increased 2.8-fold after the marathon. The activity of MAPKAPK-K2, a downstream target of p38 MAPK, increased 3.1-fold post-exercise. MSK1 and MSK2 are downstream of both ERK1/2 and p38 MAPK. MSK1 activity increased 2.4-fold post-exercise. MSK2 activity was low, relative to MSK1, with little activation post-exercise. 4. In conclusion, prolonged distance running activates MAPK signalling cascades in skeletal muscle, including increased activity of downstream targets: p90rsk, MAPKAP-K2 and MSK. Activation of these downstream targets provides a potential mechanism by which exercise induces gene transcription in skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Exercise / physiology
  • Glycogen / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • MAP Kinase Signaling System / physiology*
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • Muscle, Skeletal / enzymology*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • Ribosomal Protein S6 Kinases / metabolism
  • Ribosomal Protein S6 Kinases, 90-kDa*
  • Running / physiology*
  • p38 Mitogen-Activated Protein Kinases


  • Intracellular Signaling Peptides and Proteins
  • Glycogen
  • MAP-kinase-activated kinase 2
  • Protein-Serine-Threonine Kinases
  • RPS6KA4 protein, human
  • Ribosomal Protein S6 Kinases
  • Ribosomal Protein S6 Kinases, 90-kDa
  • mitogen and stress-activated protein kinase 1
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases