Figure 1. Activities of lipid signalling pathways during 1,25(OH)₂D₃-driven monocytic differentiation.

1,25(OH)₂D₃ crosses the cell membrane and binds to VDR in the cytosol. Ligated VDR translocates to the cell nucleus and, as a heterodimer with RXR, activates transcription of 1,25(OH)₂D₃-regulated genes. In addition, 1,25(OH)₂D₃, through an unknown mechanism, slowly activates and induces nuclear translocation of PLC isoforms. This leads to production of DAG and InsP₃ and to an increase in intracellular Ca²⁺. Another source of DAG is provided by activated PLD, followed by the action of phosphatidate phosphohydrolase (PA-OH-ase). Increased levels of DAG and Ca²⁺ cause activation of PKCα and β, which is indispensable for cell differentiation. Activation of PLA₂ causes production of prostaglandins and leukotrienes, which, through unknown mechanisms, influence monocytic cell differentiation. For references see text. Signal transduction downstream to Raf-1 will be discussed in next figures.