Calcium-dependent involucrin expression is inversely regulated by protein kinase C (PKC)α and PKCδ

Anne Deucher, Tatiana Efimova, Richard L. Eckert*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Calcium is an important physiologic regulator of keratinocyte function that may regulate keratinocyte differentiation via modulation of protein kinase C (PKC) activity. PKCα and PKCδ are two PKC isoforms that are expressed at high levels in keratinocytes. In the present study, we examine the effect of PKCδ and PKCα on calcium-dependent keratinocyte differentiation as measured by effects on involucrin (hINV) gene expression. Our studies indicate that calcium increases hINV promoter activity and endogenous hINV gene expression. This response requires PKCδ, as evidenced by the observation that treatment with dominant-negative PKCδ inhibits calcium-dependent hINV promoter activity, whereas wild type PKCδ increases activity. PKCα, in contrast, inhibits calcium-dependent hINV promoter activation, a finding that is consistent with the ability of dominant-negative PKCα and the PKCα inhibitor, Go6976, to increase hINV gene expression. The calcium-dependent regulatory response is mediated by an AP1 transcription factor-binding site located within the hINV promoter distal regulatory region that is also required for PKCδ-dependent regulation; moreover, both calcium and PKCδ produce similar, but not identical, changes in AP1 factor expression. A key question is whether calcium directly influences PKC isoform function. Our studies show that calcium does not regulate PKCα or δ levels or cause a marked redistribution to membranes. However, tyrosine phosphorylation of PKCδ is markedly increased following calcium treatment. These findings suggest that PKCα and PKCδ are required for, and modulate, calcium-dependent keratinocyte differentiation in opposing directions.

Original languageEnglish (US)
Pages (from-to)17032-17040
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number19
DOIs
StatePublished - May 10 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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