Evidence for modulation of smooth muscle force by the p38 MAP kinase/HSP27 pathway

Iliaa Yamboliev, Jason Hedges, Jack L M Mutnick, Leonard P. Adam, William T. Gerthoffer

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Mitogen-activated protein (MAP) kinases signal to proteins that could modify smooth muscle contraction. Caldesmon is a substrate for extracellular signal-related kinases (ERK) and p38 MAP kinases in vitro and has been suggested to modulate actin-myosin interaction and contraction. Heat shock protein 27 (HSP27) is downstream of p38 MAP kinases presumably participating in the sustained phase of muscle contraction. We tested the role of caldesmon and HSP27 phosphorylation in the contractile response of vascular smooth muscle by using inhibitors of both MAP kinase pathways. In intact smooth muscle, PD-098059 abolished endothelin-1 (ET-1)-stimulated phosphorylation of ERK MAP kinases and caldesmon, but p38 MAP kinase activation and contractile response remained unaffected. SB-203580 reduced muscle contraction and inhibited p38 MAP kinase and HSP27 phosphorylation but had no effect on ERK MAP kinase and caldesmon phosphorylation. In permeabilized muscle fibers, SB- 203580 and a polyclonal anti-HSP27 antibody attenuated ET-1-dependent contraction, whereas PD-098059 had no effect. These results suggest that ERK MAP kinases phosphorylate caldesmon in vivo but that activation of this pathway is unnecessary for force development. The generation of maximal force may be modulated by the p38 MAP kinase/HSP27 pathway.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume278
Issue number6 47-6
StatePublished - Jun 2000
Externally publishedYes

Fingerprint

HSP27 Heat-Shock Proteins
Calmodulin-Binding Proteins
p38 Mitogen-Activated Protein Kinases
Smooth Muscle
Mitogen-Activated Protein Kinases
Phosphotransferases
Muscle Contraction
Phosphorylation
Endothelin-1
Myosins
Vascular Smooth Muscle
Actins
Muscles
Antibodies

Keywords

  • Caldesmon
  • Endothelin-1
  • Heat shock protein 27
  • Mitogen-activated protein kinases
  • Skinned muscle fibers

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Evidence for modulation of smooth muscle force by the p38 MAP kinase/HSP27 pathway. / Yamboliev, Iliaa; Hedges, Jason; Mutnick, Jack L M; Adam, Leonard P.; Gerthoffer, William T.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 278, No. 6 47-6, 06.2000.

Research output: Contribution to journalArticle

Yamboliev, Iliaa ; Hedges, Jason ; Mutnick, Jack L M ; Adam, Leonard P. ; Gerthoffer, William T. / Evidence for modulation of smooth muscle force by the p38 MAP kinase/HSP27 pathway. In: American Journal of Physiology - Heart and Circulatory Physiology. 2000 ; Vol. 278, No. 6 47-6.
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