Role of Glucokinase in the Subcellular Localization of Glucokinase Regulatory Protein

International Journal of Molecular Sciences

Ling Jin²  Tingting Guo²  Zhixin Li⁴  Zhen Lei¹  Hui Li²  Yiqing Mao²  Xi Wang²  Na Zhou²  Yizhuang Zhang²  Ruobi Hu²  Xuehui Zhang²  Gang Niu³  David M. Irwin²  Huanran Tan² 

[1] Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China; E-Mail:;Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China; E-Mails:;Beijing N&N Genetech Company, Beijing 100082, China;Department of Integrated Traditional Chinese and Western Medicine, Peking University, Health Science Center, Beijing 100191, China; E-Mail:

关键词: protein–protein interaction;    glucokinase regulatory protein;    glucokinase;    sub-cellular localization;    glucose metabolism;   

DOI  :  10.3390/ijms16047377

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.