An important role for protein kinase C-delta in human keratinocyte migration on dermal collagen.
Migration of human keratinocytes plays a critical role in the re-epithelialization of human skin wounds, the process by which the wound bed is resurfaced and closed by keratinocytes as it forms a new epidermis. While the importance of ECM components and serum factors in the regulation of keratinocytes motility is well established, the intracellular signaling mechanisms remain fragmentary. In this study, we investigated the role of protein kinase Cdelta (PKCdelta) signaling in the promotion of human keratinocyte migration by a collagen matrix and bovine pituitary extract. We found that pharmacological inhibition of the PKCdelta pathway completely blocks migration. Using a lentivirus-based vector system, which offers more than 90% gene transduction efficiency to human keratinocytes, we show that the kinase-defective mutant of PKCdelta (K376R) dramatically inhibits human keratinocyte migration. Furthermore, PKCdelta is activated in migrating human keratinocytes. These observations indicate for the first time that the PKCdelta pathway plays an important role in the control of human keratinocyte migration.
Li
Wei
W
Department of Medicine, Norris Cancer Center, Los Angeles, California 90033, USA. wli@hsc.usc.edu
Nadelman
Celina
C
Gratch
Noah S
NS
Li
Weiquin
W
Chen
Mei
M
Kasahara
Nori
N
Woodley
David T
DT
D016475:3T3 Cells; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D020405:Dermis / Q000166:cytology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005822:Genetic Vectors / Q000235:genetics; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051745:Protein Kinase C-delta; D014161:Transduction, Genetic
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D003094:Collagen; C497259:Prkcd protein, mouse; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta