Cyclic guanosine monophosphate-dependent protein kinase I promotes adhesion of primary vascular smooth muscle cells

Mol Biol Cell. 2008 Oct;19(10):4434-41. doi: 10.1091/mbc.e08-04-0370. Epub 2008 Aug 6.

Abstract

The cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase type I (cGKI) pathway regulates many cellular functions. The current study shows that 8-Br-cGMP stimulates the number of attached primary but not that of subcultured murine vascular smooth muscle cells (VSMCs). These effects of 8-Br-cGMP require the presence of cGKI. In agreement with previous studies, cGKI inhibited the number of cells in repeatedly passaged murine VSMCs. Activation of the cGMP/cGKI pathway in freshly isolated primary VSMCs slightly decreased apoptosis and strongly increased cell adhesion. The stimulation of cell adhesion by cGKI involves an inhibition of the RhoA/Rho kinase pathway and increased exposure of beta(1) and beta(3) integrins on the cell surface. Together, these results identify a novel proadhesive function of cGMP/cGKI signaling in primary VSMCs and suggest that the opposing effects of this pathway on VSMC number depend on the phenotypic context of the cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / metabolism
  • Cell Adhesion
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism*
  • Cyclic GMP-Dependent Protein Kinases / metabolism*
  • Integrin beta1 / metabolism
  • Integrin beta3 / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Models, Biological
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / metabolism
  • Subcellular Fractions

Substances

  • Integrin beta1
  • Integrin beta3
  • Intracellular Signaling Peptides and Proteins
  • protein kinase modulator
  • 8-bromocyclic GMP
  • Cyclic GMP-Dependent Protein Kinases
  • Cyclic GMP