doi:10.1093/jb/mvj194 Disruption of Phospholipase Cd4 Gene Modulates the Liver Regeneration in Cooperation with Nuclear Protein Kinase C

Phospholipase Cd4 (PLC d4) gene has been cloned from the cDNA library of regenerating rat liver. Using PLC d4 gene–disrupted mice (PLC d4-/-), we studied a role ofPLC d4 during liver regeneration after partial hepatectomy (PH). In PLC d4-/-, liver regeneration occurred in an apparently normal way. However, BrdU-indices indicated that PLC d4 gene disruption delayed the onset of DNA synthesis by 2 h. Noticeably, the BrdU-indices inPLCd4+/+remainedratherconstantthroughoutSphase,25–35%,whereasinPLCd4-/-, it fluctuated drastically from 25 % at 34 h to 65 % at late S, 42 h after PH. This fact showed that PLC d4 gene disruption caused a higher synchronization of cell proliferation. The mRNA for PLC d4 in PLC d4+/+ appeared at late G1, and the expression continued throughout S phase. PLC activity increased transiently in chromatin at the late G1 and S phases in only PLC d4+/+, but not in PLC d4-/-. The specific increases in PLC activity well correlated with the transient increases of protein kinase C (PKC) a in chromatin of PLC d4+/+. PKC e also increased transiently in chromatin from PLC d4+/+ at late S. It is concluded that PL