Properties and regulation of glutamine transporter SN1 by protein kinases SGK and PKB.

The amino acid transporter SN1 with substrate specificity identical to the amino acid transport system N is expressed mainly in astrocytes and hepatocytes where it accomplishes Na(+)-coupled glutamine uptake and efflux. To characterize properties and regulation of SN1, substrate-induced currents and/or radioactive glutamine uptake were determined in Xenopus oocytes injected with cRNA encoding SN1, the ubiquitin ligase Nedd4-2, and/or the constitutively active serum and glucocorticoid inducible kinase S422DSGK1, its isoform SGK3, and the constitutively active protein kinase B T308D,S473DPKB. The substrate-induced currents were enhanced by increasing glutamine and/or Na(+) concentrations, hyperpolarization, and alkalinization (pH 8.0). They were inhibited by acidification (pH 6.0). Coexpression of Nedd4-2 downregulated SN1-mediated transport, an effect reversed by coexpression of S422DSGK1, SGK3, and T308D,S473DPKB. It is concluded that SN1 is a target for the ubiquitin ligase Nedd4-2, which is inactivated by the serum and glucocorticoid inducible kinase SGK1, its isoform SGK3, and protein kinase B.