Skip to main content
  • Oral presentation
  • Open access
  • Published:

Regulation of PKG expression in vascular smooth muscle cells

Type I cGMP-dependent protein kinase (PKG I) plays a major role in vascular homeostasis mediating smooth muscle relaxation in response to nitric oxide, but relatively little is known about the regulation of PKG I expression. Rho family GTPases (including RhoA and Rac1) are regulated by growth factors and cell adhesion molecules and modulate cell proliferation and motility as well as gene expression. We found opposing effects of RhoA and Rac1 on PKG I expression: (i) cell density-induced increases in PKG I expression occurred under conditions of high Rac1 activity and low RhoA activity in post-confluent cells; (ii) activation of RhoA by calpeptin suppressed PKG I, whereas down-regulation of RhoA by siRNA increased PKG I expression; and (iii) PKG I promoter activity was suppressed in cells expressing active RhoA or Rho-kinase, but was enhanced in cells expressing active Rac1, a dominant negative RhoA, or p120 catenin. Sp1 consensus sequences in the PKG I promoter were required for Rho regulation and bound nuclear proteins in a cell density-dependent manner, including the Krüppel-like factor 4 (KLF4). KLF4 was identified as the major trans-acting factor at two proximal SP1 sites; active RhoA suppressed KLF4 DNA binding and transactivation potential on the PKG I promoter. We propose a novel mechanism for cell density-dependent regulation of gene expression involving Rho and Rac; moreover, suppression of PKG I expression by RhoA may explain the decrease in vascular smooth muscle cell PKG I levels found in some models of hypertension and vascular injury.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Renate B Pilz.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Zeng, Y., Pilz, R.B. Regulation of PKG expression in vascular smooth muscle cells. BMC Pharmacol 5 (Suppl 1), S16 (2005).

Download citation

  • Published:

  • DOI: