The serine/threonine kinases SGK1, 3 and PKB stimulate the amino acid transporter ASCT2.
The human Na(+)-dependent neutral amino acid transporter type 2 (hASCT2/SLC1A5) plays an important role in the transport of neutral amino acids in epithelial cells. The serine and threonine kinases SGK1-3 and protein kinase B have been implicated in the regulation of several members of the SLC1 transporter family by enhancing their plasma membrane abundance. The present study explored whether those kinases modulate hASCT2. In Xenopus oocytes heterologously expressing hASCT2, coexpression of constitutively active (S422D)SGK1, (S419D)SGK3 or (T308DS473D)PKB upregulated the transporter activity. The stimulation requires the catalytical activity of the kinases since the inactive mutants (K127N)SGK1, (K191N)SGK3, and (T308AS473A)PKB failed to modulate the transporter. According to kinetic analysis and chemiluminescence assays, SGK1 and SGK3 modulate hASCT2 by enhancing the transporter abundance in the plasma membrane. As SGK1, 3 and PKB are activated by insulin and IGF1, the described mechanisms presumably participate in the hormonal stimulation of cellular amino acid uptake.
Palmada
Monica
M
Department of Physiology I, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany.
Speil
Andreas
A
Jeyaraj
Sankarganesh
S
Böhmer
Christoph
C
Lang
Florian
F
D026962:Amino Acid Transport System ASC / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine / Q000378:metabolism; D014981:Xenopus; D000099184:Serum-Glucocorticoid Regulated Kinases
D026962:Amino Acid Transport System ASC; D017874:Immediate-Early Proteins; D007527:Isoenzymes; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; D000099184:Serum-Glucocorticoid Regulated Kinases; C420506:SLC1A5 protein, human