Figure 8. A model of 1,25(OH)2D and calcium regulated keratinocyte differentiation. The G-protein coupled calcium receptor (CaR) when activated by extracellular calcium activates G as described in the legend to figure 6. G stimulates PLC mediated hydrolysis of PIP2 to IP3 and DG. IP3 releases Cai from intracellular stores, and DG activates PKC. Depletion of intracellular calcium stores leads to influx of calcium across store operated calcium channels. PKC stimulation leads to activation of AP-1 transcription factors which along with calcium and 1,25(OH)2D activated transcription factors stimulate the expression of genes essential for the differentiation process. 1,25(OH)2D regulates this process by inducing CaR and PLC as well as genes essential for cornified envelope formation such as involucrin and transglutaminase.