PMID- 10601273
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 52
DP  - 1999 Dec 24
TI  - Nuclear import of hepatic glucokinase depends upon glucokinase regulatory
      protein, whereas export is due to a nuclear export signal sequence in
      glucokinase.
PG  - 37125-30
AB  - 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.
FAU - Shiota, C
AU  - Shiota C
AD  - Department of Molecular Physiology, Vanderbilt University School of Medicine,
      Nashville, Tennessee 37232, USA.
FAU - Coffey, J
AU  - Coffey J
FAU - Grimsby, J
AU  - Grimsby J
FAU - Grippo, J F
AU  - Grippo JF
FAU - Magnuson, M A
AU  - Magnuson MA
LA  - eng
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - DK42502/DK/NIDDK NIH HHS/United States
GR  - DK42612/DK/NIDDK NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (GCKR protein, human)
RN  - 0 (Protein Sorting Signals)
RN  - 0 (Proteins)
RN  - 0 (glucokinase regulatory protein)
RN  - EC 2.7.1.2 (Glucokinase)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Biological Transport
MH  - *Carrier Proteins
MH  - Cell Nucleus/*enzymology
MH  - Glucokinase/chemistry/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Liver/*enzymology
MH  - *Protein Sorting Signals
MH  - Proteins/*physiology
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1074/jbc.274.52.37125 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 24;274(52):37125-30. doi: 10.1074/jbc.274.52.37125.