Ganglioside GQ1b-induced terminal differentiation in cultured mouse keratinocytes. Phosphoinositide turnover forms the onset signal.
Investigations were undertaken to see whether mouse keratinocyte differentiation was elicited by gangliosides. Among the gangliosides tested only GQ1b, a tetrasialoganglioside containing two disialosyl residues, induced keratinocyte differentiation, as indicated by the formation of cornified envelopes, enhancement of transglutaminase activity and suppression of DNA synthesis. Upon stimulation with GQ1b the mass content of Ins(1,4,5)P3 and the intracellular Ca2+ levels were markedly enhanced in a time- and dose-dependent manner, whereas no significant changes were observed with other gangliosides, thereby indicating activation of phospholipase C for the onset of keratinocyte differentiation. Furthermore, only GQ1b promoted the translocation of protein kinase C (PKC) from cytosol to membrane. Inhibition of PKC with H-7 or down-regulation of the enzyme by prolonged pre-treatment with phorbol 12,13-dibutyrate greatly suppressed transglutaminase activity and formation of cornified envelopes induced by GQ1b. These results demonstrate that the tetrasialoganglioside GQ1b generates the initial differentiation signal in mouse keratinocytes through phosphoinositide turnover, and also suggest that PKC activation may act at certain, as yet unidentified, stages of differentiation processes.
Department of Biochemistry, Gifu University School of Medicine, Japan.
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Yada
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Okano
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Nozawa
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005732:Gangliosides / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010716:Phosphatidylinositols / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D011503:Transglutaminases / Q000187:drug effects / Q000378:metabolism
D005732:Gangliosides; D006133:Growth Substances; D007546:Isoquinolines; D010716:Phosphatidylinositols; D010879:Piperazines; C039129:GQ1b ganglioside; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015544:Inositol 1,4,5-Trisphosphate; D004247:DNA; D011503:Transglutaminases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium