Signal transduction in the onset of terminal keratinocyte differentiation induced by 1 alpha,25-dihydroxyvitamin D3: role of protein kinase C translocation.
We have investigated the possible involvement of phosphoinositide turnover in the keratinocyte differentiation induced by 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3]. The mass contents of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol and intracellular calcium level were measured in murine keratinocytes stimulated with 1 alpha,25(OH)2D3 or its derivatives. Although production of these second messengers was enhanced, there were no significant differences in time- and dose-dependences between 1 alpha,25(OH)2D3 and its derivatives. These vitamin D3 compounds promoted the translocation from the cytosol to membrane of protein kinase C (PKC). Despite such common profiles in the early signal transduction parameters, only 1 alpha,25(OH)2D3 induced formation of a cornified envelope characteristic of keratinocyte differentiation. Down-regulation of PKC by prolonged pretreatment with PDBu or inhibition of the enzyme with H-7 caused marked suppression of 1 alpha,25(OH)2D3-induced formation of cornified envelopes. These findings imply that PKC is necessary but not sufficient for the onset of terminal differentiation by 1 alpha,25(OH)2D3, and also that another as yet unspecified signal generated specifically by the active vitamin D3 is required for keratinocyte differentiation.
Yada
Y
Y
Department of Biochemistry, Gifu University School of Medicine, Japan.
Ozeki
T
T
Meguro
S
S
Mori
S
S
Nozawa
Y
Y
D000818:Animals; D000831:Animals, Newborn; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004075:Diglycerides / Q000032:analysis; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000032:analysis; D007633:Keratins / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D004075:Diglycerides; D007295:Inositol Phosphates; D007633:Keratins; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D002117:Calcitriol; D002118:Calcium