Interleukin-3-mediated cell survival signals include phosphatidylinositol 3-kinase-dependent translocation of the glucose transporter GLUT1 to the cell surface

Johanne Bentley, Dalina Itchayanan, Kay Barnes, Elizabeth McIntosh, Xiuwen Tang, C. Peter Downes, Geoffrey D. Holman, Anthony D. Whetton, P. Jane Owen-Lynch, Stephen A. Baldwin

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Maintenance of glucose uptake is a key component in the response of hematopoietic cells to survival factors. To investigate the mechanism of this response we employed the interleukin-3 (IL-3)-dependent murine mast cell line IC2.9. In these cells, hexose uptake decreased markedly upon withdrawal of IL-3, whereas its readdition led to rapid (t1/2 ∼ 10 min) stimulation of transport, associated with an ∼4-fold increase in Vmax but no change in Km. Immunocytochemistry and photoaffinity labeling revealed that IL-3 caused translocation of intracellular GLUT1 transporters to the cell surface, whereas a second transporter isoform, GLUT3, remained predominantly intracellular. The inhibitory effects of latrunculin B and jasplakinolide, and of nocodazole and colchicine, respectively, revealed a requirement for both the actin and microtubule cytoskeletons in GLUT1 translocation and transport stimulation. Both IL-3 stimulation of transport and GLUT1 translocation were also prevented by the phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002. The time courses for activation of phosphatidylinositol 3-kinase and its downstream target, protein kinase B, by IL-3 were consistent with a role in IL-3-induced transporter translocation and enhanced glucose uptake. We conclude that one component of the survival mechanisms elicited by IL-3 involves the subcellular redistribution of glucose transporters, thus ensuring the supply of a key metabolic substrate.

Original languageEnglish
Pages (from-to)39337-39348
Number of pages12
JournalJournal of Biological Chemistry
Volume278
Issue number41
DOIs
Publication statusPublished - 10 Oct 2003
Externally publishedYes

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