Cyclic GMP-dependent protein kinase. targeting and control of expression

Thomas M. Lincoln, Hassan Sellak, Nupur Dey, Chung Sik Choi, Felricia Brown

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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-1? 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.

Original languageEnglish (US)
Title of host publicationHandbook of Cell Signaling, 2/e
PublisherElsevier Inc.
Pages1471-1477
Number of pages7
Volume2
ISBN (Print)9780123741455
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Cyclic GMP-dependent protein kinase. targeting and control of expression'. Together they form a unique fingerprint.

  • Cite this

    Lincoln, T. M., Sellak, H., Dey, N., Choi, C. S., & Brown, F. (2010). Cyclic GMP-dependent protein kinase. targeting and control of expression. In Handbook of Cell Signaling, 2/e (Vol. 2, pp. 1471-1477). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-374145-5.00180-7