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- W2770290923 abstract "Publisher Summary This chapter addresses three aspects of PKG function that include the role of PKG-I targeting to subcellular proteins especially in smooth muscle cells (SMC), the role of PKG-I in regulating vascular SMC (VSMC) gene expression, and the regulation of the expression of PKG-I. The serum response factor (SRF) interacts with numerous co-transcriptional regulators, including myocardin, a smooth muscle specific co-transcription factor and member of the larger myocardin-related factor (MRF) family of proteins. PKG-I enhances myocardin-stimulated SRF activity in part through the phosphorylation of a myocardin regulatory protein, cysteine-rich protein-2 (CRP-2) in VSMC. The enhanced myocardin-dependent SRF activity in a non-smooth muscle cell line is observed, when it is transfected with myocardin and PKG-I cDNA. PKG-I also increases SRF binding to smooth muscle-specific promoter regions of SMMHC and SM22. The Kruppel-like factor (KLF-4) binds to the Sp1 sites on the PKG-I proximal promoter and regulates gene transcription. The small molecular weight G proteins, RhoA and rac, regulate KLF-4 binding and PKG-I gene expression. The inflammatory, atherogenic cytokines such as IL-1β and TNFα decrease PKG-I mRNA and protein levels in bovine aortic VSMC. One mechanism responsible for this event is a cytokine-dependent increase in iNOS expression, NO biosynthesis, and a decrease in Sp1 binding to the PKG-I promoter. Suppression of iNOS activity or sGC activity inhibits the downregulation of PKG-I mRNA induced by the cytokines. PKA inhibition also suppresses the effects of cytokines on PKG-I mRNA expression, suggesting that high elevations in cGMP in response to iNOS expression cross-activate PKA and lead to decreased Sp1 protein binding to the PKG-I promoter." @default.
- W2770290923 created "2017-12-04" @default.
- W2770290923 creator A5003596090 @default.
- W2770290923 creator A5018518980 @default.
- W2770290923 creator A5026598574 @default.
- W2770290923 creator A5036973484 @default.
- W2770290923 creator A5038891678 @default.
- W2770290923 date "2010-01-01" @default.
- W2770290923 modified "2023-09-26" @default.
- W2770290923 title "Cyclic GMP-Dependent Protein Kinase" @default.
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