Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: From the regulation of tone to gene expression

T. M. Lincoln, N. Dey, Hassan Sellak

Research output: Contribution to journalReview article

380 Citations (Scopus)

Abstract

cGMP is a second messenger that produces its effects by interacting with intracellular receptor proteins. In smooth muscle cells, one of the major receptors for cGMP is the serine/ threonine protein kinase, cGMP-dependent protein kinase (PKG). PKG has been shown to catalyze the phosphorylation of a number of physiologically relevant proteins whose function it is to regulate the contractile activity of the smooth muscle cell. These include proteins that regulate free intracellular calcium levels, the cytoskeleton, and the phosphorylation state of the regulatory light chain of smooth muscle myosin. Other studies have shown that vascular smooth muscle cells (VSMCs) that are cultured in vitro may cease to express PKG and will, coincidentally, acquire a noncontractile, synthetic phenotype. The restoration of PKG expression to the synthetic phenotype VSMC results in the cells acquiring a more contractile phenotype. These more recent studies suggest that PKG controls VSMC gene expression that, in turn, regulates phenotypic modulation of the cells. Therefore, the regulation of PKG gene expression appears to be linked to phenotypic modulation of VSMC. Because several vascular disorders are related to the accumulation of synthetic, fibropro-liferative VSMC in the vessel wall, it is likely that changes in the activity of the nitric oxide/cGMP/PKG pathway is involved the development of these diseases.

Original languageEnglish (US)
Pages (from-to)1421-1430
Number of pages10
JournalJournal of Applied Physiology
Volume91
Issue number3
StatePublished - Sep 12 2001

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Cyclic GMP-Dependent Protein Kinases
Smooth Muscle Myocytes
Smooth Muscle
Vascular Smooth Muscle
Gene Expression
Phenotype
Phosphorylation
Smooth Muscle Myosins
Proteins
Protein-Serine-Threonine Kinases
Gene Expression Regulation
Second Messenger Systems
Cytoskeleton
Blood Vessels
Nitric Oxide
Calcium
Light

Keywords

  • Nitric oxide
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Invited review : cGMP-dependent protein kinase signaling mechanisms in smooth muscle: From the regulation of tone to gene expression. / Lincoln, T. M.; Dey, N.; Sellak, Hassan.

In: Journal of Applied Physiology, Vol. 91, No. 3, 12.09.2001, p. 1421-1430.

Research output: Contribution to journalReview article

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