title: Steroid-sensitive gene 1 is a novel cyclic GMP-dependent protein kinase I substrate in vascular smooth muscle cells.
abstract: 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.
authors.affiliation: Molecular Cardiology Research Institute and Division of Cardiology, Tufts Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: Guang-rong
authors.initials: GR
authors.lastname: Wang
authors.forename: Howard K
authors.initials: HK
authors.lastname: Surks
authors.forename: K Mary
authors.initials: KM
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Mendelsohn
authors.forename: Robert M
authors.initials: RM
authors.lastname: Blanton
mesh_terms: D002478:Cells, Cultured; D006152:Cyclic GMP / Q000235:genetics / Q000378:metabolism*; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000235:genetics / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D026403:S-Nitrosothiols / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C492631:CCDC80 protein, human; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D025521:Tumor Suppressor Proteins; C021315:S-nitrosocysteine; D062965:Cyclic GMP-Dependent Protein Kinase Type I; C569718:PRKG1 protein, human; D006152:Cyclic GMP; D003545:Cysteine
keywords: Cardiovascular Disease; Protein Kinase G (PKG); Signal Transduction; Steroid-sensitive Gene 1; Vascular Biology; Vascular Smooth Muscle Cells