AJP - Cell Physiology, Vol 263, Issue 3 C714-C719, Copyright © 1992 by American Physiological Society
Ca(2+)-independent isoforms of protein kinase C differentially translocate in smooth muscle
R. A. Khalil, C. Lajoie, M. S. Resnick and K. G. Morgan
Cardiovascular Division, Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02215.
It is generally assumed that smooth muscle contraction is dependent on
changes in intracellular Ca2+ concentration ([Ca2+]i); however, we have
previously reported that alpha-agonist-induced contraction of aorta smooth
muscle cells can occur in the absence of changes in [Ca2+]i [Collins, E.
M., M. P. Walsh, and K. G. Morgan. Am. J. Physiol. 262 (Heart Circ.
Physiol. 31): H754-H762, 1992]. The mechanism of this [Ca2+]i-independent
contraction is controversial. We have now identified the Ca(2+)-independent
protein kinase C (PKC) isoforms epsilon and zeta in ferret aorta and have
used digital imaging microscopy to determine their subcellular
distribution. At rest, epsilon-PKC is diffusely distributed in the cytosol,
whereas zeta-PKC is concentrated in the perinuclear region; both isoforms
are excluded from the nuclear space. Agonist stimulation causes a
[Ca2+]i-independent translocation of epsilon-PKC to the surface membrane
and of zeta-PKC to the intranuclear compartment. In comparison, ferret
portal vein cells, which display a totally Ca(2+)-dependent agonist
contraction, are lacking in epsilon-PKC but display perinuclear zeta-PKC,
which translocates intranuclearly on activation. Thus the
Ca(2+)-independent vascular contraction appears to be associated with
plasmalemmal translocation of epsilon-PKC; in contrast, the intranuclear
translocation of zeta-PKC may function in control of gene expression.
