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Staurosporine Induces a Sequential Program of Mouse Keratinocyte Terminal Differentiation through Activation of PKC Isozymes.
- Source :
-
Journal of Investigative Dermatology . Mar1996, Vol. 106 Issue 3, p482-489. 8p. - Publication Year :
- 1996
-
Abstract
- Staurosporine (stsp) induces assembly of cornified envelopes in mouse keratinocyte cultures. To clarify whether this effect is the consequence of a coordinated differentiation program similar to that observed in epidermis, we assessed the expression of multiple differentiation-specific markers in stsp-treated keratinocytes. In medium containing 0.05 mM Ca&sup2+; in which the basal cell phenotype is normally maintained, stsp induced dose-dependent increases in keratin 1, epidermal and keratinocyte transglutaminases, SPR-1, loricrin, and profilaggrin mRNA. Based on nuclear run-on analysis, stsp-mediated marker expression was found to be due at least in part to increased transcription. Since protein kinase C (PKC) activation is required for keratinocyte differentiation, we tested whether stsp influenced this signaling pathway. Stsp induced the translocation of multiple PKC isoforms from the cytosol to membrane and/or cytoskeletal fractions, inducing isozyme downregulation within 24 h. Moreover, AP-1 DNA binding activity was elevated in stsp-treated keratinocytes, consistent with the notion that this agent influences keratinocyte-specific gene expression via the PKC pathway. Stsp-mediated marker expression was inhibited by the PKC inhibitor GF 109203X. In cells pre-treated with bryostatin 1 to selectively down-modulate specific PKC isoforms, stsp-induced loricrin, filaggrin, and SPR-1 expression was suppressed when PKC α, ϵ, and/or δ were downregulated, suggesting that these isozymes may be necessary for marker expression in response to this agent. Thus, in addition to its effects on cornified envelope assembly, stsp induces a coordinate program of differentiation-specific keratinocyte gene expression that is mediated at least in part by the PKC signaling pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0022202X
- Volume :
- 106
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Investigative Dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 12343690
- Full Text :
- https://doi.org/10.1111/1523-1747.ep12343690