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Sustained phospholipase D activation is associated with keratinocyte differentiation
E M Jung1, S Betancourt-Calle, R Mann-Blakeney
1Program in Cell Signaling, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta 30912-2630, USA.
Carcinogenesis
|May 1, 1999
Summary
Phospholipase D (PLD) activation is key to epidermal keratinocyte differentiation. Sustained PLD activity, induced by agents like TPA and staurosporine (Stsp), drives keratinocyte differentiation, while bradykinin shows transient effects.
Area of Science:
- Dermatology
- Cell Biology
- Biochemistry
Background:
- Epidermal growth and differentiation involve complex signaling pathways.
- Phospholipase D (PLD) has been implicated in regulating keratinocyte functions.
- Understanding the role of PLD in keratinocyte differentiation is crucial for skin biology.
Purpose of the Study:
- To investigate the effects of agents modulating keratinocyte growth and differentiation on PLD activation.
- To determine the relationship between PLD activation patterns and keratinocyte differentiation markers.
- To elucidate the role of PLD in mediating keratinocyte differentiation.
Main Methods:
- Primary mouse epidermal keratinocytes were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), staurosporine (Stsp), and bradykinin.
- PLD activity was measured acutely and over extended periods.
- Transglutaminase activity, a marker of late differentiation, was assessed.
- Cell proliferation was also monitored.
Main Results:
- TPA induced acute and sustained PLD activation.
- Stsp showed no acute PLD activation but induced sustained activation after prolonged treatment, which was additive with TPA.
- Bradykinin caused transient acute PLD activation.
- Both TPA and Stsp increased transglutaminase activity, indicating late differentiation, while bradykinin had minimal effect.
- Bradykinin did not significantly affect cell proliferation.
Conclusions:
- Sustained activation of PLD is associated with the induction of keratinocyte differentiation.
- PLD activity may mediate late keratinocyte differentiation via diacylglycerol generation and protein kinase C (PKC) isoform activation.
- TPA rapidly drives keratinocytes to late differentiation through potent PLD stimulation.
- Stsp's gradual PLD activation may facilitate a differentiation pattern similar to in vivo skin.