Ca(2+)-independent isoforms of protein kinase C differentially translocate in smooth muscle.
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.
Khalil
R A
RA
Cardiovascular Division, Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02215.
Lajoie
C
C
Resnick
M S
MS
Morgan
K G
KG
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology; D001692:Biological Transport; D002118:Calcium / Q000502:physiology; D005289:Ferrets; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D011169:Portal Vein / Q000166:cytology / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism*; D014018:Tissue Distribution
D007527:Isoenzymes; D011493:Protein Kinase C; D002118:Calcium