A protein kinase C agonist, selective for the beta I isozyme, induces E-selectin and VCAM-1 expression on HUVEC but does not translocate PKC.
A protein kinase C (PKC) agonist selective for the beta I isozyme, 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), induced NF-kappa B-like binding activity and surface expression of E-selectin and VCAM-1 in human umbilical vein endothelial cells (HUVEC), similar to the effects of tumor necrosis factor-alpha (TNF-alpha). Induction of E-selectin and VCAM-1 expression by dPPA was completely inhibited by the PKC inhibitors staurosporine and Ro31-7549. The PKC inhibitors also reduce TNF-alpha-induced VCAM-1 expression. However, neither dPPA nor TNF-alpha translocated PKC from the cytosolic to the plasma or nuclear membrane particulate fractions in HUVEC. These results indicate that activation of the beta I PKC isozyme is sufficient for expression of E-selectin and VCAM-1, and suggest that PKC may mediate the effects of TNF-alpha and dPPA without requiring the translocation normally associated with activation of PKC.
Deisher
T A
TA
Department of Medicine/Division of Hematology, University of Washington, Seattle 98195.
Sato
T T
TT
Pohlman
T H
TH
Harlan
J M
JM
D000470:Alkaloids / Q000494:pharmacology; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D015345:Oligonucleotide Probes; D010703:Phorbol Esters / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1
D000470:Alkaloids; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D010703:Phorbol Esters; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C029704:12-deoxyphorbolphenylacetate; C080287:thymeleatoxin; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; C064755:Ro 31-7549