PKCα induces differentiation through ERK1/2 phosphorylation in mouse keratinocytes

Haeng Ran Seo, Yoo Wook Kwan, Chul Koo Cho, Sangwoo Bae, Sy Jae Lee, Jae Won Soh, Hee Yong Chung, Yun Sil Lee

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Epidermal keratinocyte differentiation is a tightly regulated stepwise process that requires protein kinase C (PKC) activation. Studies on cultured mouse keraitnocytes induced to differentiate with Ca2+ have indirectly implicated the involvement of PKCα isoform. When PKCα was overexpressed in undifferentiated keratinocytes using adenoviral system, expressions of differentiation markers such as loricrin, filaggrin, keratin 1 (MK1) and keratin 10 (MK10) were increased, and ERK1/2 phosphorylation was concurrently induced without change of other MAPK such as p38 MAPK and JNK1/2. Similarly, transfection of PKCα kinase active mutant (PKCα-CAT) in the undifferentiated keratinocyte, but not PKCβ-CAT, also increased differentiation marker expressions. On the other hand, PKCα dominant negative mutant (PKCβ-KR) reduced Ca2+-mediated differentiation marker expressions, while PKCβ-KR did not, suggesting that PKCα is responsible for keratinocyte differentiation. When downstream pathway of PKCα in Ca2+-mediated differentiation was examined, ERK1/2, p38 MAPK and JNK1/2 phosphorylations were increased by Ca2+ shift. Treatment of keratinocytes with PD98059, MEK inhibitor, and SB20358, p38 MAPK inhibitor, before Ca2+ shift induced morphological changes and reduced expressions of differentiation markers, but treatment with SP60012, JNK1/2 inhibitor, did not change at all. Dominant negative mutants of ERK1/2 and p38 MAPK also inhibited the expressions of differentiation marker expressions in Ca2+ shifted cells. The above results indicate that both ERK1/2 and p38 MAPK may be involved in Ca2+-mediated differentiation, and that only ERK1/2 pathway is specific for PKCα-mediated differentiation in mouse keratinocytes.

Original languageEnglish
Pages (from-to)292-299
Number of pages8
JournalExperimental and Molecular Medicine
Issue number4
StatePublished - 31 Aug 2004


  • Ca-mediated differentiation
  • ERK1/2
  • Mouse keratinocytes
  • PKCα
  • p38 MAPK


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