A new phospholipase C delta 4 is induced at S-phase of the cell cycle and appears in the nucleus.
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 delta 4) encoding a polypeptide of 770 amino acids with structural similarity to PLC delta-type isozymes was isolated. PLC delta 4 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 delta 4 is dominantly present in nucleus. Nuclear PLC delta 4 dramatically increases at the transition from G1- to S-phase, and the high content continues to the end of M-phase. PLC delta 4 almost disappears when cells re-enter the next G1-phase. On the other hand, the contents of PLC beta 1, PLC gamma 1, and PLC delta 1 do not change significantly during the cell cycle. These results suggest that PLC delta 4 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.
Department of Molecular Oncology, University of Tokyo, Japan.
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N
Liu
K
K
Fukami
H
H
Yu
T
T
Takenawa
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001769:Blood; D002467:Cell Nucleus / Q000201:enzymology*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008115:Liver Regeneration; D051379:Mice; D008969:Molecular Sequence Data; D054803:Phospholipase C delta; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016196:S Phase; D010738:Type C Phospholipases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D007527:Isoenzymes; D012333:RNA, Messenger; D010738:Type C Phospholipases; D054803:Phospholipase C delta; C518025:Plcd1 protein, mouse; C518026:Plcd1 protein, rat; C518031:Plcd4 protein, mouse; C518032:Plcd4 protein, rat