title: Stimulation of the amino acid transporter SLC6A19 by JAK2.
abstract: JAK2 (Janus kinase-2) is expressed in a wide variety of cells including tumor cells and contributes to the proliferation and survival of those cells. The gain of function mutation (V617F)JAK2 mutant is found in the majority of myeloproliferative diseases. Cell proliferation depends on the availability of amino acids. Concentrative cellular amino acid uptake is in part accomplished by Na(+) coupled amino acid transport through SLC6A19 (B(0)AT). The present study thus explored whether JAK2 activates SLC6A19. To this end, SLC6A19 was expressed in Xenopus oocytes with or without wild type JAK2, (V617F)JAK2 or inactive (K882E)JAK2 and electrogenic amino acid transport determined by dual electrode voltage clamp. In SLC6A19-expressing oocytes but not in oocytes injected with water or JAK2 alone, the addition of leucine (2mM) to the bath generated a current (I(le)), which was significantly increased following coexpression of JAK2 or (V617F)JAK2, but not by coexpression of (K882E)JAK2. Coexpression of JAK2 enhanced the maximal transport rate without significantly modifying the affinity of the carrier. Exposure of the oocytes to the JAK2 inhibitor AG490 (40μM) resulted in a gradual decline of I(le). According to chemiluminescence JAK2 enhanced the carrier protein abundance in the cell membrane. The decline of I(le) following inhibition of carrier insertion by brefeldin A (5μM) was similar in the absence and presence of JAK2 indicating that JAK2 stimulates carrier insertion into rather than inhibiting carrier retrival from the cell membrane. In conclusion, JAK2 up-regulates SLC6A19 activity which may foster amino acid uptake into JAK2 expressing cells.
authors.affiliation: Department of Physiology I, University of Tübingen, Germany.
authors.forename: Shefalee K
authors.initials: SK
authors.lastname: Bhavsar
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Hosseinzadeh
authors.forename: Katja
authors.initials: K
authors.lastname: Merches
authors.forename: Shuchen
authors.initials: S
authors.lastname: Gu
authors.forename: Stefan
authors.initials: S
authors.lastname: Bröer
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D014981:Xenopus
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D000596:Amino Acids; C491436:SLC6A19 protein, human; D020126:Brefeldin A; C507924:JAK2 protein, human; D053614:Janus Kinase 2