RGD Reference Report - Nuclear import of hepatic glucokinase depends upon glucokinase regulatory protein, whereas export is due to a nuclear export signal sequence in glucokinase.

General

Nuclear import of hepatic glucokinase depends upon glucokinase regulatory protein, whereas export is due to a nuclear export signal sequence in glucokinase.
Authors:	Shiota, C Coffey, J Grimsby, J Grippo, JF Magnuson, MA
Citation:	Shiota C, etal., J Biol Chem. 1999 Dec 24;274(52):37125-30.
RGD ID:	8554356
Pubmed:	PMID:10601273 (View Abstract at PubMed)
Hepatic glucokinase (GK) moves between the nucleus and cytoplasm in response to metabolic alterations. Here, using heterologous cell systems, we have found that at least two different mechanisms are involved in the intracellular movement of GK. In the absence of the GK regulatory protein (GKRP) GK resides only in the cytoplasm. However, in the presence of GKRP, GK moves to the nucleus and resides there in association with this protein until changes in the metabolic milieu prompt its release. GK does not contain a nuclear localization signal sequence and does not enter the nucleus in a GKRP-independent manner because cells treated with leptomycin B, a specific inhibitor of leucine-rich NES-dependent nuclear export, do not accumulate GK in the nucleus. Instead, entry of GK into the nucleus appears to occur via a piggy-back mechanism that involves binding to GKRP. Nuclear export of GK, which occurs after its release from GKRP, is due to a leucine-rich nuclear export signal within the protein ((300)ELVRLVLLKLV(310)). Thus, GKRP appears to function as both a nuclear chaperone and metabolic sensor and is a critical component of a hepatic GK translocation cycle for regulating the activity of this enzyme in response to metabolic alterations.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
protein import into nucleus	involved_in	IDA		8554356	PMID:10601273	BHF-UCL

Cellular Component

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
cytoplasm	located_in	IDA		8554356; 8554356	PMID:10601273	BHF-UCL
nucleus	located_in	IDA		8554356; 8554356	PMID:10601273	BHF-UCL

Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
protein binding	enables	IPI	UniProtKB:Q07071	8554356	PMID:10601273	BHF-UCL
protein binding	enables	IPI	UniProtKB:P17712	8554356	PMID:10601273	BHF-UCL

Objects Annotated

Genes (Rattus norvegicus)

Gck (glucokinase)

Gckr (glucokinase regulator)

Additional Information

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Nuclear import of hepatic glucokinase depends upon glucokinase regulatory protein, whereas export is due to a nuclear export signal sequence in glucokinase.