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Int. J. Mol. Sci. 2015, 16(4), 7377-7393; doi:10.3390/ijms16047377

Role of Glucokinase in the Subcellular Localization of Glucokinase Regulatory Protein

1
Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China
2
Department of Integrated Traditional Chinese and Western Medicine, Peking University, Health Science Center, Beijing 100191, China
3
Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China
4
Beijing N&N Genetech Company, Beijing 100082, China
5
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
*
Authors to whom correspondence should be addressed.
Academic Editor: Bing Yan
Received: 19 January 2015 / Revised: 3 March 2015 / Accepted: 18 March 2015 / Published: 2 April 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [3748 KB, uploaded 2 April 2015]   |  

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. View Full-Text
Keywords: protein–protein interaction; glucokinase regulatory protein; glucokinase; sub-cellular localization; glucose metabolism protein–protein interaction; glucokinase regulatory protein; glucokinase; sub-cellular localization; glucose metabolism
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Jin, L.; Guo, T.; Li, Z.; Lei, Z.; Li, H.; Mao, Y.; Wang, X.; Zhou, N.; Zhang, Y.; Hu, R.; Zhang, X.; Niu, G.; Irwin, D.M.; Tan, H. Role of Glucokinase in the Subcellular Localization of Glucokinase Regulatory Protein. Int. J. Mol. Sci. 2015, 16, 7377-7393.

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