cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the
regulation of tone to gene expression.
Lincoln, Thomas M., Nupur Dey, and Hassan Sellak.
Department of Pathology, Division of Molecular and Cellular Pathology, University
of Alabama at Birmingham, Birmingham, Alabama 35294«hyphen»0019
APStracts 8:0332A, 2001.
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, fibroproliferative 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.
APS Manuscript Number A537-1.
Article publication pending J Appl Physiol
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 29 June 2001