Steroid-sensitive Gene 1 Is a Novel Cyclic GMP-dependent Protein Kinase I Substrate in Vascular Smooth Muscle Cells

• Published in: The Journal of biological chemistry Vol. 288; no. 34; pp. 24972 - 24983
• Main Authors: Wang, Guang-rong, Surks, Howard K., Tang, K. Mary, Zhu, Yan, Mendelsohn, Michael E., Blanton, Robert M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.08.2013; American Society for Biochemistry and Molecular Biology
• Subjects: Cardiovascular Disease; 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; Protein Kinase G (PKG); S-Nitrosothiols - pharmacology; Signal Transduction; Steroid-sensitive Gene 1; Tumor Suppressor Proteins - biosynthesis; Tumor Suppressor Proteins - genetics; Vascular Biology; Vascular Smooth Muscle Cells; Cardiovascular Disease; Vascular Smooth Muscle Cells; Steroid-sensitive Gene 1; Signal Transduction; Vascular Biology; Protein Kinase G (PKG)
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.456244

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. Background: Protein kinase GI (PKGI) regulates multiple cardiovascular processes, but its effectors remain incompletely understood. Results: We identified steroid-sensitive gene 1 (SSG1) as being regulated by PKG in vascular cells. Conclusion: SSG1 functions as a PKGI kinase target and interacting partner in cardiovascular tissues. Significance: Identifying new PKGI effectors may improve the understanding of the pathophysiology of cardiovascular diseases.