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Glucokinase regulatory protein is essential for the proper subcellular localisation of liver glucokinase
Author(s) -
de la Iglesia Núria,
Veiga-da-Cunha Maria,
Van Schaftingen Emile,
Guinovart Joan J.,
Ferrer Juan C.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00971-0
Subject(s) - glucokinase , cytosol , subcellular localization , xenopus , cytoplasm , green fluorescent protein , intracellular , microbiology and biotechnology , biochemistry , nuclear transport , nucleus , hepatocyte , biology , cell nucleus , chemistry , enzyme , gene , in vitro
Glucokinase (GK), a key enzyme in the glucose homeostatic responses of the liver, changes its intracellular localisation depending on the metabolic status of the cell. Rat liver GK and Xenopus laevis GK, fused to the green fluorescent protein (GFP), concentrated in the nucleus of cultured rat hepatocytes at low glucose and translocated to the cytoplasm at high glucose. Three mutant forms of Xenopus GK with reduced affinity for GK regulatory protein (GKRP) did not concentrate in the hepatocyte nuclei, even at low glucose. In COS‐1 and HeLa cells, a blue fluorescent protein (BFP)‐tagged version of rat liver GK was only able to accumulate in the nucleus when it was co‐expressed with GKRP‐GFP. At low glucose, both proteins concentrated in the nuclear compartment and at high glucose, BFP‐GK translocated to the cytosol while GKRP‐GFP remained in the nucleus. These findings indicate that the presence of and binding to GKRP are necessary and sufficient for the proper intracellular localisation of GK and directly involve GKRP in the control of the GK subcellular distribution.