Steroid-sensitive gene 1 is a novel cyclic GMP-dependent protein kinase I substrate in vascular smooth muscle cells

J Biol Chem. 2013 Aug 23;288(34):24972-83. doi: 10.1074/jbc.M113.456244. Epub 2013 Jul 6.


NO, via its second messenger cGMP, activates protein kinase GI (PKGI) to induce vascular smooth muscle cell relaxation. The mechanisms by which PKGI kinase activity regulates cardiovascular function remain incompletely understood. Therefore, to identify novel protein kinase G substrates in vascular cells, a λ phage coronary artery smooth muscle cell library was constructed and screened for phosphorylation by PKGI. The screen identified steroid-sensitive gene 1 (SSG1), which harbors several predicted PKGI phosphorylation sites. We observed direct and cGMP-regulated interaction between PKGI and SSG1. In cultured vascular smooth muscle cells, both the NO donor S-nitrosocysteine and atrial natriuretic peptide induced SSG1 phosphorylation, and mutation of SSG1 at each of the two predicted PKGI phosphorylation sites completely abolished its basal phosphorylation by PKGI. We detected high SSG1 expression in cardiovascular tissues. Finally, we found that activation of PKGI with cGMP regulated SSG1 intracellular distribution.

Keywords: Cardiovascular Disease; Protein Kinase G (PKG); Signal Transduction; Steroid-sensitive Gene 1; Vascular Biology; Vascular Smooth Muscle Cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cells, Cultured
  • Cyclic GMP / genetics
  • Cyclic GMP / metabolism*
  • Cyclic GMP-Dependent Protein Kinase Type I / genetics
  • Cyclic GMP-Dependent Protein Kinase Type I / metabolism*
  • Cysteine / analogs & derivatives
  • Cysteine / pharmacology
  • Extracellular Matrix Proteins
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Glycoproteins / biosynthesis*
  • Glycoproteins / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Phosphorylation / drug effects
  • Phosphorylation / physiology
  • S-Nitrosothiols / pharmacology
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics


  • CCDC80 protein, human
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Nitric Oxide Donors
  • S-Nitrosothiols
  • Tumor Suppressor Proteins
  • S-nitrosocysteine
  • Cyclic GMP-Dependent Protein Kinase Type I
  • PRKG1 protein, human
  • Cyclic GMP
  • Cysteine