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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.
Bentley, J, Itchayanan, D, Barnes, K, McIntosh, E, Tang, X, Downes, C, Holman, G, Whetton, A, Owen-Lynch, P, Baldwin, S
J Biol Chem. 2003;278( 41):39337-48.
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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(1/2) approximately 10 min) stimulation of transport, associated with an approximately 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.
Keyword(s)
Animals; Biological Transport, Active; Cell Line; Kinetics; Mice; Nerve Tissue Proteins; Protein-Serine-Threonine Kinases; Research Support, Non-U.S. Gov't; Signal Transduction; antagonists & inhibitors: 1-Phosphatidylinositol 3-Kinase; drug effects: Cell Survival; metabolism: Actins; metabolism: Cell Membrane; metabolism: Cytoskeleton; metabolism: Deoxyglucose; metabolism: Glucose; metabolism: Interleukin-3; metabolism: Microtubules; metabolism: Monosaccharide Transport Proteins; metabolism: Proto-Oncogene Proteins; pharmacology: Androstadienes; pharmacology: Chromones; pharmacology: Enzyme Inhibitors; pharmacology: Morpholines; pharmacology: Recombinant Proteins