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 βI isozyme, 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), induced NF-κB-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-α (TNF-α). 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-α induced VCAM-1 expression. However, neither dPPA nor TNF-α translocated PKC from the cytosolic to the plasma or nuclear membrane particulate fractions in HUVEC. These results indicate that activation of the βI PKC isozyme is sufficient for expression of E-selectin and VCAM-1, and suggest that PKC may mediate the effects of TNF-α and dPPA without requiring the translocation normally associated with activation of PKC. © 1993 Academic Press.