Activation of protein kinase C inhibits human keratinocyte migration.
The involvement of protein kinase C (PKC) in epidermal growth factor (EGF)-induced human keratinocyte migration was studied with the phagokinetic assay. It was concluded that PKC activation does not mediate, but rather inhibits, EGF-induced keratinocyte migration. The following experimental observations support these conclusions: 1) The PKC inhibitor H-7 did not inhibit EGF-induced migration but instead led to a modest enhancement. 2) PKC activators such as phorbol-12-myristate-13-acetate (PMA), phorbol-12,13-dibutyrate (PDBu), and 1,2-dioctanoly-sn-glycerol inhibited migration, but biologically inactive 4 alpha-PMA had no effect. 3) PMA did not inhibit keratinocyte attachment and spreading but blocked migration almost immediately after addition. 4) Migration of PKC-depleted cells, which were produced by prolonged treatment with PDBu, was enhanced similarly to normal cells by EGF. 5) PKC-depleted cells were not susceptible to the inhibitory effects of phorbol esters on migration. Additional experiments, in which cells were preactivated with EGF, suggested that PKC inhibits the EGF effect at a post-receptor level. The inhibitory effect of PKC on keratinocyte migration was not restricted to EGF-induced migration; PKC activation also inhibited keratinocyte migration induced by bovine pituitary extract, insulin, insulin-like growth factor-1, and keratinocyte growth factor.
Ando
Y
Y
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia 19104-6142.
Lazarus
G S
GS
Jensen
P J
PJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002396:Catechols / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D004357:Drug Synergism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D015603:Keratinocytes / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020032:Tyrphostins
D002396:Catechols; D006133:Growth Substances; D007546:Isoquinolines; D009570:Nitriles; D010703:Phorbol Esters; D010879:Piperazines; D020032:Tyrphostins; C060152:tyrphostin 47; D004815:Epidermal Growth Factor; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C