| Proteolytic processing of cGMP-dependent protein kinase I mediates nuclear cGMP signaling in vascular smooth muscle cells. | |
| | |
MedLine Citation:
|
PMID: 18535260 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Cyclic GMP modulates gene expression in vascular smooth muscle cells (SMCs) in part by stimulating cGMP-dependent protein kinase I (PKGI) and the phosphorylation of transcription factors. In some cells, cGMP increases nuclear translocation of PKGI and PKGI-dependent phosphorylation of transcription regulators; however, these observations have been variable, and the mechanisms mediating nuclear PKGI translocation are incompletely understood. We tested the hypothesis that proteolytic cleavage of PKGI is required for cGMP-stimulated nuclear compartmentation of PKGI and phosphorylation of transcription factors. We detected an NH(2)-terminal PKGI fragment with leucine zipper domain immunoreactivity in the cytosol and endoplasmic reticulum of SMCs, but only a COOH-terminal PKGI fragment containing the catalytic region (now termed PKGIgamma) was observed in the Golgi apparatus (GA) and nucleoplasm. Posttranslational PKGI processing in the GA was critical for nuclear compartmentation of PKGIgamma because GA disruption with nocodazol or brefeldin A inhibited PKGIgamma nuclear localization. PKGIgamma immunoreactivity was particularly abundant in the nucleolus of interphase SMCs where its colocalization with the nucleolar dense fibrillar component protein fibrillarin closely matched the level of nucleolar assembly. Purified nucleolar PKGIgamma enzyme activity was insensitive to cGMP stimulation, which is consistent with its lack of the NH(2)-terminal autoinhibitory domain. Mutation of a putative proteolytic cleavage region in PKGI inhibited cGMP-mediated phosphorylation of cAMP response element-binding protein, cAMP response element-dependent transcription, and nuclear localization of PKGIgamma. These observations suggest that posttranslational modification of PKGI critically influences the nuclear translocation of PKGI and activities of cGMP in SMCs. |
| | |
Authors:
|
Takahiro Sugiura; Hidehiko Nakanishi; Jesse D Roberts |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-06-05 |
Journal Detail:
|
Title: Circulation research Volume: 103 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2008 Jul |
Date Detail:
|
Created Date: 2008-07-03 Completed Date: 2008-07-29 Revised Date: 2012-02-03 |
Medline Journal Info:
|
Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
|
Languages: eng Pagination: 53-60 Citation Subset: IM |
Affiliation:
|
Cardiovascular Research Center, Departments of Anesthesia, Massachusetts General Hospital, Boston and Harvard Medical School, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Active Transport, Cell Nucleus
/
drug effects,
physiology Animals Antineoplastic Agents / pharmacology Brefeldin A / pharmacology Cell Nucleolus / enzymology*, genetics Cyclic AMP / genetics, metabolism Cyclic GMP / genetics, metabolism* Cyclic GMP-Dependent Protein Kinases / genetics, metabolism* Cytoplasm / enzymology Golgi Apparatus / enzymology, genetics Muscle, Smooth, Vascular / enzymology* Mutation Myocytes, Smooth Muscle / enzymology* Nocodazole / pharmacology Phosphorylation / drug effects Protein Processing, Post-Translational* / drug effects, genetics Protein Structure, Tertiary / genetics Protein Synthesis Inhibitors / pharmacology Rats Response Elements / genetics Signal Transduction / physiology* |
| Grant Support | |
ID/Acronym/Agency:
|
HL080316/HL/NHLBI NIH HHS; R01 HL080316-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Protein Synthesis Inhibitors; 20350-15-6/Brefeldin A; 31430-18-9/Nocodazole; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP; EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases; EC 2.7.11.12/cGMP-dependent protein kinase I |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Nrf2 regulates antioxidant gene expression evoked by oxidized phospholipids in endothelial cells and...
Next Document: Nuclear shape, mechanics, and mechanotransduction.