Thromboxane prostanoid receptor signals through Gi protein to rapidly activate extracellular signal-regulated kinase in human airways

Simona Citro, Saula Ravasi, G. Enrico Rovati, Valérie Capra

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

We showed previously that activation of the thromboxane prostanoid (TP) receptor causes human airway smooth muscle (HASM) cells to proliferate, suggesting a role in airway remodeling. This study aimed at determining the molecular mechanisms underlying this mitogenic action. We found that the MEK inhibitor PD98059 significantly affected agonist-induced DNA synthesis of HASM cells, which suggests that extracellular signal-regulated kinases (ERK) are involved. ERK activation by the agonist U46619 was rapid, sensitive to pertussis toxin, and significantly abrogated by the tyrosine kinase inhibitors genistein and PP1. Stimulation of the TP receptor was also found to translocate phosphorylated ERK into the nucleus. TP receptor was found to activate Ras, as demonstrated by inhibition of ERK activation and DNA synthesis by Clostridium sordellii lethal toxin, and by the ability of U46619 to increase RasGTP. Finally, [3H]thymidine incorporation and ERK phosphorylation were also affected by prior treatment with protein kinase C inhibitor GF109203X, although to different extents. In conclusion, in HASM cells TP receptor, predominantly coupled to Gi/o proteins, activates the Ras/ERK pathway to induce mitogenesis, probably with the involvement of nonreceptor tyrosine kinases and protein kinase C.

Original languageEnglish
Pages (from-to)326-333
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume32
Issue number4
DOIs
Publication statusPublished - Apr 2005

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Thromboxane Receptors
Thromboxanes
Extracellular Signal-Regulated MAP Kinases
Prostaglandins
Smooth Muscle Myocytes
Muscle
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Proteins
Chemical activation
Protein Kinase C
Airway Remodeling
ras Proteins
Phosphorylation
Protein C Inhibitor
Genistein
DNA
Mitogen-Activated Protein Kinase Kinases
Pertussis Toxin
Protein Kinase Inhibitors
Protein-Tyrosine Kinases

Keywords

  • Cell proliferation
  • Human airway smooth muscle
  • MAP kinase
  • Ras
  • Thromboxane A receptor

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Thromboxane prostanoid receptor signals through Gi protein to rapidly activate extracellular signal-regulated kinase in human airways. / Citro, Simona; Ravasi, Saula; Rovati, G. Enrico; Capra, Valérie.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 32, No. 4, 04.2005, p. 326-333.

Research output: Contribution to journalArticle

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