SGK1 kinase upregulates GLUT1 activity and plasma membrane expression.
Phosphatidylinositol 3-kinase (PI3 kinase) inhibition disrupts the ability of insulin to stimulate GLUT1 and GLUT4 translocation into the cell membrane and thus glucose transport. The effect on GLUT4 but not on GLUT1 is mediated by activation of protein kinase B (PKB). The serum- and glucocorticoid-inducible kinase SGK1, a further kinase downstream of PI3 kinase, regulates several transporters by enhancing their plasma membrane abundance. GLUT1 contains a consensus site ((95)Ser) for phosphorylation by SGK1. Thus, the present study investigated whether GLUT1 is regulated by the kinase. Tracer-flux studies in Xenopus oocytes and HEK-293 cells demonstrated that GLUT1 transport is enhanced by constitutively active (S422D)SGK1. The effect requires the kinase catalytical activity since the inactive mutant (K127N)SGK1 failed to modulate GLUT1. GLUT1 stimulation by (S422D)SGK1 is not due to de novo protein synthesis but rather to an increase of the transporter's abundance in the plasma membrane. Kinetic analysis revealed that SGK1 enhances maximal transport rate without altering GLUT1 substrate affinity. These observations suggest that SGK1 regulates GLUT1 and may contribute to or account for the PI3 kinase-dependent but PKB-independent stimulation of GLUT1 by insulin.
Palmada
Monica
M
Institute of Physiology I, University of Tübingen, Germany.
Boehmer
Christoph
C
Akel
Ahmad
A
Rajamanickam
Jeyaganesh
J
Jeyaraj
Sankarganesh
S
Keller
Konrad
K
Lang
Florian
F
D017667:Adipocytes; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009865:Oocytes; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction; D015854:Up-Regulation; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
D003847:Deoxyglucose; D005947:Glucose; D051272:Glucose Transporter Type 1; D017874:Immediate-Early Proteins; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C495677:SLC2A1 protein, human