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Protein Kinase C Regulates Keratinocyte Transglutaminase (TGK) Gene Expression in Cultured Primary Mouse Epidermal Keratinocytes Induced to Terminally Differentiate by Calcium.

Protein Kinase C Regulates Keratinocyte Transglutaminase (TGK) Gene Expression in Cultured Primary Mouse Epidermal Keratinocytes Induced to Terminally Differentiate by Calcium.

Authors :
Dlugosz, Andrzej A.
Yuspa, Stuart H.
Source :
Journal of Investigative Dermatology. Apr94, Vol. 102 Issue 4, p409-414. 6p.
Publication Year :
1994

Abstract

During the final stage of epidermal differentiation, activation of keratinocyte transglutaminase results in covalent cross-linking of a variety of proteins to form highly protective cornified cell envelopes. We have studied the regulation of keratinocyte transglutaminase (TGK) gene expression in murine epidermal keratinocytes induced to terminally differentiate <em>in vitro</em> by increasing the level of extracellular Ca++ or treatment with the protein kinase C (PKC) activator 12- O-tetradecanoylphorbol-13-acetate (TPA). Raising extracellular Ca++ induces squamous differentiation of cultured keratinocytes and elicits a concentration-dependent increase in expression of TGK mRNA; keratinocytes grown for 24 h in 0.12 mM Ca++ medium express ∼12 times as much TGK mRNA as basal cells (grown in 0.05 mM Ca++ medium), whereas cultures exposed to 1.4 mM Ca++ express ∼17 times as much. TPA induces squamous differentiation and TGK mRNA even in basal keratinocyte cultures grown in 0.05 mM Ca++ medium, suggesting that expression of this differentiation marker is regulated by the PKC signaling pathway. Induction of TGK mRNA in response to TPA treatment is transient, reaching a peak at 6-8 h and returning to baseline by 24 h. In contrast, elevation of TGK mRNA levels in response to Ca++ persists for at least 24 h. The increased abundance of TGK mRNA reflects increased transcription of the TGK gene, based on nuclear run-on analysis of Ca++- and TPA-treated keratinocytes. Induction of TGK mRNA by either TPA or Ca++ is blocked in the presence of cycloheximide, suggesting that a PKC-dependent protein factor is required for TGK gene expression in response to both stimuli. Furthermore, the accumulation of TGK mRNA in keratinocytes treated with TPA or CA++ is blocked in cells treated with the PKC inhibitor GF 109203X or bryostatin. These results suggest that the induction of TGK gene expression by CA++ is dependent on PKC, providing further support for the hypothesis that PKC plays a central role in regulating the late stages of epidermal differentiation. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0022202X
Volume :
102
Issue :
4
Database :
Academic Search Index
Journal :
Journal of Investigative Dermatology
Publication Type :
Academic Journal
Accession number :
12372171
Full Text :
https://doi.org/10.1111/1523-1747.ep12372171