A new phospholipase C δ4 is induced at S-phase of the cell cycle and appears in the nucleus

Abstract

To discover a new phospholipase C (PLC) related to cell growth, we screened a cDNA library prepared from regenerating rat liver. A novel PLC (PLC δ4) encoding a polypeptide of 770 amino acids with structural similarity to PLC δ-type isozymes was isolated. PLC δ4 mRNA is expressed more remarkably in regenerating liver than in normal resting liver. It is also distributed abundantly in tumor cells such as hepatoma and src- transformed cells. Furthermore, its expression can be induced markedly by serum treatment and reaches a maximum at 8 h. Western blot analysis and immunocytochemical staining showed that PLC δ4 is dominantly present in nucleus. Nuclear PLC δ4 dramatically increases at the transition from G1- to S-phase, and the high content continues to the end of M-phase. PLC δ4 almost disappears when cells re-enter the next G1-phase. On the other hand, the contents of PLC β1, PLC γ1, and PLC δ1 do not change significantly during the cell cycle. These results suggest that PLC δ4 is expressed in nucleus in response to mitogenic stimulation and plays important roles in cell growth as one of the early genes expressed during the transition from G1- to S-phase in the cell cycle.