Growth factor-induced promoter activation of murine phospholipase C delta 4 gene

Phospholipase C delta 4 (PLC delta 4) is one of the delta-type PLC isozymes, the expression of which is induced in nuclei by treatment with serum and also in some cancer cells. We isolated and analyzed a promoter region of the murine PLC delta 4 gene. DNA sequence analysis showed that this region is GC-rich and has no TATA box, and the region from -143 to -127 was found, by luciferase activity and gel mobility-shift assay, to be essential for transcription of PLC delta 4. We also found that the promoter activity of PLC delta 4 was stimulated by treatment with growth factors such as bradykinin, lysophosphatidic acid, and Ca2+ ionophore in addition to serum. In parallel, we detected PLC delta 4 mRNA induction and an increase in complex formation of the promoter region and nuclear protein from HeLa cells on stimulation with these growth factors. Finally, we found that trapping the growth factor-induced cytoplasmic Ca2+-inhibited activation of the promoter activity and protein induction in nuclei. These results show that PLC delta 4 may have an important role in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+.