Phosphorylation of caldesmon by ERK MAP kinases in smooth muscle

Jason C. Hedges, Brian C. Oxhorn, Michael Carty, Leonard P. Adam, Ilia A. Yamboliev, William T. Gerthoffer

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


Phosphorylation of h-caldesmon has been proposed to regulate airway smooth muscle contraction. Both extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinases phosphorylate h-caldesmon in vitro. To determine whether both enzymes phosphorylate caldesmon in vivo, phosphorylation-site-selective antibodies were used to assay phosphorylation of MAP kinase consensus sites. Stimulation of cultured tracheal smooth muscle cells with ACh or platelet-derived growth factor increased caldesmon phosphorylation at Ser789 by about twofold. Inhibiting ERK MAP kinase activation with 50 μM PD-98059 blocked agonist-induced caldesmon phosphorylation completely. Inhibiting p38 MAP kinases with 25 μM SB-203580 had no effect on ACh-induced caldesmon phosphorylation. Carbachol stimulation increased caldesmon phosphorylation at Ser789 in intact tracheal smooth muscle, which was blocked by the M2 antagonist AF-DX 116 (1 μM). AF-DX 116 inhibited carbachol-induced isometric contraction by 15 ± 1.4%, thus dissociating caldesmon phosphorylation from contraction. Activation of M2 receptors leads to activation of ERK MAP kinases and phosphorylation of caldesmon with little or no functional effect on isometric force. P38 MAP kinases are also activated by muscarinic agonists, but they do not phosphorylate caldesmon in vivo.

Original languageEnglish (US)
Pages (from-to)C718-C726
JournalAmerican Journal of Physiology - Cell Physiology
Issue number4 47-4
StatePublished - 2000
Externally publishedYes


  • Carbachol
  • Extracellular signal-regulated kinase
  • PD-98059
  • SB- 203580
  • Trachea
  • p38 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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