Signal transduction in the onset of terminal keratinocyte differentiation induced by 1 alpha,25-dihydroxyvitamin D3: role of protein kinase C translocation
Yada, Y.; Ozeki, T.; Meguro, S.; Mori, S.; Nozawa, Y.
Biochemical and Biophysical Research Communications 163(3): 1517-1522
1989
ISSN/ISBN: 0006-291X PMID: 2476989 Document Number: 338451
We have investigated the possible involvement of phospoinositide turonover 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.