Journal of Biochemistry Advance Access published online on September 23, 2006
Journal of Biochemistry, doi:10.1093/jb/mvj194
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1 Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466 8550; Department of Molecular Pathology, Aichi Cancer Center Institute, 1-1, Kanokoden, Chikusa-ku, Nagoya 464-8681
* To whom correspondence should be addressed. Phospholipase C
Received June 22, 2006
Accepted September 5, 2006
Regular Paper
Disruption of Phospholipase C
Atsushi Akutagawa 1, Kiyoko Fukami 2, Yoshiko Banno 3, Tadaomi Takenawa 4, Reiji Kannagi 5, Yukihiro Yokoyama 6, Koji Oda 6, Masato Nagino 6, Yuji Nimura 6, Shonen Yoshida 7, and Keiko Tamiya-Koizumi 8 *
4 Gene Modulates the Liver Regeneration in Cooperation with Nuclear Protein Kinase C
2 Laboratory of Genome and Biosignal, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji-shi, Tokyo 192-0392
3 Department of Cell Signaling, Gifu University, Graduate School of Medicine, 1-1, Yanagido, Gifu 501-1194
4 Division of Biochemistry, Department of Cancer biology, Institute of Medical Science, University of Tokyo, 4-6-1, Shiroganedai, Minato-ku, Tokyo 108-8639
5 Department of Molecular Pathology, Aichi Cancer Center Institute, 1-1, Kanokoden, Chikusa-ku, Nagoya 464-8681
6 Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466 8550
7 Nagoya Kyoritsu Hospital, 1-172, Hokke, Nakagawa-ku, Nagoya 454-8525
8 Department of Molecular Pathology, Aichi Cancer Center Institute, 1-1, Kanokoden, Chikusa-ku, Nagoya 464-8681; Nagoya University School of Health Sciences, Nagoya University Graduate School of Medicine, 1-1-20, Daiko-minami, Higashi-ku, Nagoya 461-8673
Keiko Tamiya-Koizumi, E-mail: kkoizumi{at}met.nagoya-u.ac.jp
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Abstract
4 (PLC
4) gene has been cloned from the cDNA library of regenerating rat liver. Using PLC
4 gene-disrupted mice (PLC
4-/-), we studied a role of PLC
4 during liver regeneration after partial hepatectomy (PH). In PLC
4-/-, liver regeneration occurred in an apparently normal way. However, BrdU-indices indicated that PLC
4 gene disruption delayed the onset of DNA synthesis by 2 h. Noticeably, the BrdU- indices in PLC
4+/+ remained rather constant throughout S phase, 25-35%, whereas in PLC
4-/-, it fluctuated drastically from 25% at 34 h to 65% at late S, 42 h after PH. This fact showed that PLC
4 gene disruption caused a higher synchronization of cell proliferation. The mRNA for PLC
4 in PLC
4+/+ 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
4+/+, but not in PLC
4-/-. The specific increases in PLC activity well correlated with the transient increases of protein kinase C (PKC) a in chromatin of PLC
4+/+. PKC
also increased transiently in chromatin from PLC
4+/+ at late S. It is concluded that PLC
4 regulates the liver regeneration in cooperation with nuclear PKC
and
.
4; partial hepatectomy; protein kinase C.
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