Inhibition of geranylgeranylation blocks agonist-induced actin reorganization in human airway smooth muscle cells

Ryan E. Lesh, Charles W. Emala, H. Thomas Lee, Defen Zhu, Reynold A. Panettieri, Carol A. Hirshman

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

To determine whether RhoA isoprenylation (geranylgeranylation) is required for agonist-induced actin cytoskeleton reorganization (measured by an increase in the filamentous F- to monomeric G-actin ratio), human airway smooth muscle cells were treated for 72 h with inhibitors of geranylgeranyltransferase I. Geranylgeranyltransferase inhibitor (GGTI)-2147 or -286 pretreatment completely blocked the increase in the F- to G-actin fluorescence ratio when cells were stimulated with lysophosphatidic acid (LPA), endothelin, or carbachol. In contrast, LPA or endothelin induced actin cytoskeletal reorganization in cells treated with farnesyltransferase inhibitor (FTI)-277 to inactivate Ras. Forskolin-induced adenylyl cyclase activity was inhibited by carbachol in GGTI-2147-pretreated cells, demonstrating that the effect of geranylgeranyltransferase I inhibition on stress fiber formation was not due to uncoupling of signaling between the heterotrimeric Gi protein (the Gγ subunit is isoprenylated) and distal effectors. These results demonstrate that selective GGTIs can inhibit agonist-induced actin reorganization.

Original languageEnglish (US)
Pages (from-to)L824-L831
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number4 25-4
DOIs
StatePublished - 2001

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Keywords

  • Actin depolymerization
  • Cytoskeleton
  • Fluorescence microscopy
  • Prenylation
  • Prenyltransferase inhibition

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