Nuclear transportation of diacylglycerol kinase gamma and its possible function in the nucleus.
Diacylglycerol kinases (DGKs) convert diacylglycerol (DG) to phosphatidic acid, and both lipids are known to play important roles in lipid signal transduction. Thereby, DGKs are considered to be a one of the key players in lipid signaling, but its physiological function remains to be solved. In an effort to investigate one of nine subtypes, we found that DGKgamma came to be localized in the nucleus with time in all cell lines tested while seen only in the cytoplasm at the early stage of culture, indicating that DGKgamma is transported from the cytoplasm to the nucleus. The nuclear transportation of DGKgamma didn't necessarily need DGK activity, but its C1 domain was indispensable, suggesting that the C1 domain of DGKgamma acts as a nuclear transport signal. Furthermore, to address the function of DGKgamma in the nucleus, we produced stable cell lines of wild-type DGKgamma and mutants, including kinase negative, and investigated their cell size, growth rate, and cell cycle. The cells expressing the kinase-negative mutant of DGKgamma were larger in size and showed slower growth rate, and the S phase of the cells was extended. These findings implicate that nuclear DGKgamma regulates cell cycle.
Matsubara
Takehiro
T
Laboratory of Molecular Pharmacology and Laboratory of Biochemistry, Biosignal Research Center, Rokkodai-cho 1-1, Nada-ku, Kobe 657-8501.
Shirai
Yasuhito
Y
Miyasaka
Kei
K
Murakami
Takuya
T
Yamaguchi
Yasuto
Y
Ueyama
Takehiko
T
Kai
Masahiro
M
Sakane
Fumio
F
Kanoh
Hideo
H
Hashimoto
Toshiaki
T
Kamada
Shinji
S
Kikkawa
Ushio
U
Saito
Naoaki
N
D021581:Active Transport, Cell Nucleus / Q000235:genetics / Q000502:physiology; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D048429:Cell Size; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells
D007527:Isoenzymes; D019852:Diacylglycerol Kinase