The isoenzyme of protein kinase c induces a ca2+-independent
contraction in vascular smooth muscle.
Horowitz, Arie, Odile Cl[acute]ement-Chomienne, Michael P. Walsh, and
Kathleen G. Morgan.
Program in Smooth Muscle Research, Charles A. Dana Research
Institute, Harvard-Thorndike Laboratory, Cardiovascular Division,
Beth Israel Hospital, and Department of Medicine, Harvard Medical
School, Boston, MA 02215; Boston Biomedical Research Institute,
Boston, MA 02114; Department of Medical Biochemistry, University of
Calgary, Calgary, Alberta T2N 4N1, Canada
APStracts 3:0076C, 1996.
We provide here the first direct evidence for in situ functional
specificity of PKC as a regulator of smooth muscle contractility.
Protein kinase C (PKC) is known to cause a Ca2+-independent
contraction of ferret aorta smooth muscle, and the expression of two
Ca2+-independent PKC isoenzymes, and z, has been demonstrated in this
tissue. To test directly the hypothesis that one of these isoenzymes
regulates contractility, constitutively active forms of PKC and PKCz
were applied to saponin-permeabilized single ferret aortic smooth
muscle cells. PKCz caused no significant force response, but PKC
induced contraction of a magnitude (105 +/- 8 [mu]g) similar to that
produced by phenylephrine (110 +/-10 [mu]g), a relatively selective
1-adrenergic agonist that triggers a PKC-dependent contraction. The
PKC -induced contraction was reversed by the PKC pseudosubstrate
inhibitory peptide, PKC19-31. The myosin light chain kinase inhibitor
ML-9 did not affect the force response of PKC -activated cells,
suggesting that PKC may induce this contraction solely via thin
filament disinhibition. In support of this conclusion, calponin and
caldesmon were shown to be good in vitro substrates of PKC but not of
PKCz.
Received 28 September 1995; accepted in final form 26 February
1996.
APS Manuscript Number C595-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96