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Interleukin-3-mediated Cell Survival Signals Include Phosphatidylinositol 3-Kinase-dependent Translocation of the Glucose Transporter GLUT1 to the Cell Surface.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

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  • 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
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<mark>Journal publication date</mark>10/10/2003
<mark>Journal</mark>Journal of Biological Chemistry
Issue number41
Volume278
Number of pages12
Pages (from-to)39337-39348
Publication StatusPublished
<mark>Original language</mark>English

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 (t 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.