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.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
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 DM,Tan Hdoi
10.3390/ijms16047377subject
Has Abstractpub_date
2015-04-02 00:00:00pages
7377-93issue
4issn
1422-0067pii
ijms16047377journal_volume
16pub_type
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