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

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dc.contributor.authorBogatikov, Evgenii
dc.contributor.authorMunoz, Carlos
dc.contributor.authorPakladok, Tatsiana
dc.contributor.authorAlesutan, Ioana
dc.contributor.authorShojaiefard, Manzar
dc.contributor.authorSeebohm, Guiscard
dc.contributor.authorFöller, Michael
dc.contributor.authorPalmada, Monica
dc.contributor.authorBöhmer, Christoph
dc.contributor.authorBröer, Stefan
dc.contributor.authorLang, Florian
dc.date.accessioned2014-08-20T05:58:34Z
dc.date.available2014-08-20T05:58:34Z
dc.date.issued2012
dc.date.updated2015-12-11T07:32:09Z
dc.description.abstractBackground: 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/S473APKB/Akt without or with additional expression of wild-type PIKfyve or PKB/Akt-resistant S318APIKfyve. 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 (Ile), which was significantly increased following coexpression of PKB/Akt, but not by coexpression of T308A/S473APKB/Akt. The effect of PKB/Akt was augmented by additional coexpression of PIKfyve but not of S318APIKfyve. Coexpression of PKB/Akt enhanced the maximal transport rate without significantly modifying the affinity of the carrier. The decline of Ile 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.
dc.format9 pages
dc.identifier.issn1015-8987
dc.identifier.urihttp://hdl.handle.net/1885/11955
dc.publisherKarger
dc.relationhttp://purl.org/au-research/grants/nhmrc/525415
dc.relationhttp://purl.org/au-research/grants/nhmrc/585479
dc.rightshttp://www.sherpa.ac.uk/romeo/issn/1015-8987/author can archive publisher's version/PDF, Sherpa/Romeo as at 20/8/14
dc.sourceCellular Physiology and Biochemistry 30.6 (2012): 1538-1546
dc.subjectamino acid uptake
dc.subjectPKB/Akt
dc.subjectB0AT1
dc.subjectPIKfyve
dc.titleUp-regulation of amino acid transporter SLC6A19 activity and surface protein abundance by PKB/Akt and PIKfyve
dc.typeJournal article
local.bibliographicCitation.issue6
local.bibliographicCitation.lastpage1546
local.bibliographicCitation.startpage1538
local.contributor.affiliationBröer, Stefan, The Australian National Universityen_AU
local.contributor.authoremailflorian.lang@uni-tuebingen.deen_AU
local.contributor.authoremailstefan.broeer@anu.edu.auen_AU
local.contributor.authoruidu4009041en_AU
local.identifier.absfor111600 - MEDICAL PHYSIOLOGY
local.identifier.ariespublicationf5625xPUB2530
local.identifier.citationvolume30
local.identifier.doi10.1159/000343341
local.identifier.essn1421-9778en_AU
local.identifier.scopusID2-s2.0-84870749150
local.identifier.thomsonID000314149200020
local.identifier.uidSubmittedByu4009041en_AU
local.publisher.urlhttp://www.karger.com/en_AU
local.type.statusPublished Versionen_AU

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