The ras-binding domain of ral GDS-like protein-2 as a ras inhibitor in smooth muscle cells

Thomas H. Fischer, Julie Brittain, Lorenza Trabalzini, Albert J. Banes, Gilbert C. White, Carr J. Smith, Timothy C. Nichols

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

This study was undertaken to determine whether the response of smooth muscle cells to mitogens can be inhibited by inactivating ras with the ral GDS like protein-2 ras-binding domain (RGL2-RBD). RGL2 is a member of the ral GDS family of proteins that contains a carboxy terminal ras-binding domain which binds the GTP ligated form of ras and rap and a CDC25 homology domain with the structural features of a guanine nucleotide exchange factor. The effect of ras signaling on the smooth muscle cell growth factor response was studied using rat aortic A10 smooth muscle cells transfected with a plasmid that encoded the RGL2-RBD. RGL2-RBD transfection resulted in a 12-fold reduction in the number of clonal colonies that were obtained after selection, and dramatically slowed cell cycle progression. RGBL2-RBD reduced DNA synthesis and inhibited platelet derived growth factor (PDGF)-mediated activation of the MAPK pathway. These findings indicated that interfering with ras signaling inhibits smooth muscle cell proliferation and raise the possibility that ras signaling inhibition might be used therapeutically to control smooth muscle proliferation after vascular injury.

Original languageEnglish (US)
Pages (from-to)934-940
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume305
Issue number4
DOIs
StatePublished - Jun 13 2003

Keywords

  • Growth factor
  • Proliferation
  • Ral GDS-like protein-2
  • Ras
  • Smooth muscle cells

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Fischer, T. H., Brittain, J., Trabalzini, L., Banes, A. J., White, G. C., Smith, C. J., & Nichols, T. C. (2003). The ras-binding domain of ral GDS-like protein-2 as a ras inhibitor in smooth muscle cells. Biochemical and Biophysical Research Communications, 305(4), 934-940. https://doi.org/10.1016/S0006-291X(03)00878-7