title: Role of glucokinase in the subcellular localization of glucokinase regulatory protein.
abstract: Glucokinase (GCK) is the rate-limiting enzyme of liver glucose metabolism. Through protein-protein interactions, glucokinase regulatory protein (GCKR) post-transcriptionally regulates GCK function in the liver, and causes its nuclear localization. However the role of GCK in regulating GCKR localization is unknown. In the present study, using in vitro and in vivo models, we examined the levels of GCK and GCKR, and their subcellular localization. We found that total cellular levels of GCKR did not vary in the in vivo models, but its subcellular localization did. In animals with normal levels of GCK, GCKR is mainly localized to the nuclei of hepatocytes. In seven-day old rats and liver-specific Gck gene knockout mice (animals that lack or have reduced levels of GCK protein), GCKR was found primarily in the cytoplasm. The interaction of GCK with GCKR was further examined using in vitro models where we varied the levels of GCK and GCKR. Varying the level of GCK protein had no effect on total cellular GCKR protein levels. Taken together, our results indicate that GCK is important for the localization of GCKR to the nucleus and raises the possibility that GCKR may have functions in addition to those regulating GCK activity in the cytoplasm.
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. jinling@bjmu.edu.cn.
authors: Ling
authors: L
authors: Jin
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. ttguo@bjmu.edu.cn.
authors: Tingting
authors: T
authors: Guo
authors: Department of Integrated Traditional Chinese and Western Medicine, Peking University, Health Science Center, Beijing 100191, China. leezhixin@tom.com.
authors: Zhixin
authors: Z
authors: Li
authors: Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. lei1153@163.com.
authors: Zhen
authors: Z
authors: Lei
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. lihui@bjmu.edu.cn.
authors: Hui
authors: H
authors: Li
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. maoyiqing@bjmu.edu.cn.
authors: Yiqing
authors: Y
authors: Mao
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. xixi1125@bjmu.edu.cn.
authors: Xi
authors: X
authors: Wang
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. zhouna@bjmu.edu.cn.
authors: Na
authors: N
authors: Zhou
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. onepiecezyz1989@163.com.
authors: Yizhuang
authors: Y
authors: Zhang
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. huruobi@bjmu.edu.cn.
authors: Ruobi
authors: R
authors: Hu
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. xuehuizhang@bjmu.edu.cn.
authors: Xuehui
authors: X
authors: Zhang
authors: Beijing N&N Genetech Company, Beijing 100082, China. nngene@sohu.com.
authors: Gang
authors: G
authors: Niu
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. david.irwin@utoronto.ca.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada. david.irwin@utoronto.ca.
authors: David M
authors: DM
authors: Irwin
authors: Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China. tanlab@bjmu.edu.cn.
authors: Huanran
authors: H
authors: Tan
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats
chemical_list: D002352:Carrier Proteins; C080906:glucokinase regulatory protein; D005941:Glucokinase; D005947:Glucose