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XB-ART-46334
Cell Physiol Biochem 2012 Jan 01;306:1538-46. doi: 10.1159/000343341.
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Up-regulation of amino acid transporter SLC6A19 activity and surface protein abundance by PKB/Akt and PIKfyve.

Bogatikov E , Munoz C , Pakladok T , Alesutan I , Shojaiefard M , Seebohm G , Föller M , Palmada M , Böhmer C , Bröer S , Lang F .


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BACKGROUND: The amino acid transporter B0AT1 (SLC6A19) accomplishes concentrative cellular uptake of neutral amino acids. SLC6A19 is stimulated by serum- & glucocorticoid-inducible kinase (SGK) isoforms. SGKs are related to PKB/Akt isoforms, which also stimulate several amino acid transporters. PKB/Akt modulates glucose transport in part by phosphorylating and thus activating phosphatidylinositol-3-phosphate-5-kinase (PIKfyve), which fosters carrier protein insertion into the cell membrane. The present study explored whether PKB/Akt and/or PIKfyve stimulate SLC6A19. METHODS: SLC6A19 was expressed in Xenopus oocytes with or without wild-type PKB/Akt or inactive (T308A/S473A)PKB/Akt without or with additional expression of wild-type PIKfyve or PKB/Akt-resistant (S318A)PIKfyve. Electrogenic amino acid transport was determined by dual electrode voltage clamping. RESULTS: In SLC6A19-expressing oocytes but not in water-injected oocytes, the addition of the neutral amino acid L-leucine (2 mM) to the bath generated a current (I(le)), which was significantly increased following coexpression of PKB/Akt, but not by coexpression of (T308A/S473A)PKB/Akt. The effect of PKB/Akt was augmented by additional coexpression of PIKfyve but not of (S318A)PIKfyve. Coexpression of PKB/Akt enhanced the maximal transport rate without significantly modifying the affinity of the carrier. The decline of I(le) following inhibition of carrier insertion by brefeldin A (5 µM) was similar in the absence and presence of PKB/Akt indicating that PKB/Akt stimulated carrier insertion into rather than inhibiting carrier retrieval from the cell membrane. CONCLUSION: PKB/Akt up-regulates SLC6A19 activity, which may foster amino acid uptake into PKB/Akt-expressing epithelial and tumor cells.

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Species referenced: Xenopus
Genes referenced: akt1 pikfyve slc6a19