Up-regulation of amino acid transporter SLC6A19 activity and surface protein abundance by PKB/Akt and PIKfyve

Evgenii Bogatikov, Carlos Munoz, Tatsiana Pakladok, Ioana Alesutan, Manzar Shojaiefard, Guiscard Seebohm, Michael Föller, Monica Palmada, Christoph Böhmer, Stefan Bröer, Florian Lang*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    34 Citations (Scopus)

    Abstract

    Background: The amino acid transporter B 0 AT1 (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 wildtype 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 signifcantly 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 signifcantly modifying the affnity 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.

    Original languageEnglish
    Pages (from-to)1538-1546
    Number of pages9
    JournalCellular Physiology and Biochemistry
    Volume30
    Issue number6
    DOIs
    Publication statusPublished - Dec 2012

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