Upregulation of Na-coupled glucose transporter SGLT1 by Tau tubulin kinase 2

Abstract

The Tau-tubulin-kinase 2 (TTBK2) is a serine/threonine kinase expressed in various tissues including tumors. Up-regulation of TTBK2 increases resistance of tumor cells against antiangiogenic treatment and confers cell survival. Tumor cell survival critically depends on cellular uptake of glucose, which is partially accomplished by SGLT1 (SLC5A1) mediated Na(+)-coupled glucose transport. The present study explored whether TTBK2 participates in the regulation of SGLT1 activity. To this end, electrogenic glucose transport was determined in Xenopus oocytes expressing SGLT1 with or without wild-type TTBK2, truncated TTBK2([1-450]) or kinase inactive mutants TTBK2-KD and TTBK2-KD([1-450]). TTBK2, but not TTBK2([1-450]), TTBK2-KD or TTBK2-KD([1-450]), increased membrane carrier protein abundance and electrogenic glucose transport capacity in SGLT1-expressing Xenopus oocytes. Thus TTBK2 is a completely novel regulator of Na(+)-coupled glucose transport.