1,25-Dihydroxyvitamin D-3,D- phospholipase D and protein kinase C in keratinocyte differentiation

1,25-Dihydroxyvitamin D-3, thought to be a physiological regulator of epide rmal keratinocyte growth and differentiation, also elicits the complete dif ferentiative program in vitro, with expression of various genes;proteins ch aracteristic of both early and late differentiation. 1,25-Dihydroxyvitamin D-3 functions by interacting with an intracellular receptor that binds to D NA at vitamin D response elements (VDRE) thereby affecting transcription. 1 ,25-Dihydroxyvitamin D-3 has been demonstrated to alter the expression of s everal enzymes involved in signal transduction, and presumably this is the mechanism through which the hormone regulates differentiation. It has recen tly been shown that 1,25-dihydroxyvitamin D-3 specifically increases the ex pression/activity of phospholipase D-1, an enzyme that hydrolyzes phospholi pids to generate lipid messengers, such as diacylglycerol (DAG). DAG, in tu rn, is known to activate several members of the protein kinase C (PKC) fami ly. It has been proposed that this signaling pathway mediates late differen tiation events in epidermal keratinocytes. In this article the data support ing a role for PKC and phospholipase D in keratinocyte differentiation, as well as in the pathogenesis of skin diseases, are reviewed and a model is p roposed for the signaling pathways that regulate this process upon exposure to 1,25-dihydroxyvitamin D-3. (C) 2000 Elsevier Science Ireland Ltd. All r ights reserved.