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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


Reference:

Bentley, J., Itchayanan, D., Barnes, K., McIntosh, E., Tang, X. W., Downes, C. P., Holman, G. D., Whetton, A. D., Owen-Lynch, P. J. and Baldwin, S. A., 2003. Interleukin-3-mediated cell survival signals include phosphatidylinositol 3-kinase-dependent translocation of the glucose transporter GLUT1 to the cell surface. Journal of Biological Chemistry, 278 (41), pp. 39337-39348.

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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) similar to 10 min) stimulation of transport, associated with an similar to4-fold increase in V-max 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.

Details

Item Type Articles
CreatorsBentley, J., Itchayanan, D., Barnes, K., McIntosh, E., Tang, X. W., Downes, C. P., Holman, G. D., Whetton, A. D., Owen-Lynch, P. J. and Baldwin, S. A.
DOI10.1074/jbc.M305689200
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code4134
Additional InformationID number: ISI:000185713800011

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