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

J Bentley, D Itchayanan, K Barnes, E McIntosh, X W Tang, C P Downes, G D Holman, A D Whetton, P J Owen-Lynch, S A Baldwin

Research output: Contribution to journalArticle

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

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Phosphatidylinositol 3-Kinase
Facilitative Glucose Transport Proteins
Interleukin-3
Cell Survival
Cells
jasplakinolide
Nocodazole
Glucose
Proto-Oncogene Proteins c-akt
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Hexoses
Colchicine
Actin Cytoskeleton
Mast Cells
Microtubules
Labeling
Actins
Protein Isoforms
Chemical activation
Immunohistochemistry

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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 W; Downes, C P; Holman, G D; Whetton, A D; Owen-Lynch, P J; Baldwin, S A.

In: Journal of Biological Chemistry, Vol. 278, No. 41, 2003, p. 39337-39348.

Research output: Contribution to journalArticle

Bentley, J, Itchayanan, D, Barnes, K, McIntosh, E, Tang, XW, Downes, CP, Holman, GD, Whetton, AD, Owen-Lynch, PJ & Baldwin, SA 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, vol. 278, no. 41, pp. 39337-39348. https://doi.org/10.1074/jbc.M305689200
Bentley, J ; Itchayanan, D ; Barnes, K ; McIntosh, E ; Tang, X W ; Downes, C P ; Holman, G D ; Whetton, A D ; Owen-Lynch, P J ; Baldwin, S A. / Interleukin-3-mediated cell survival signals include phosphatidylinositol 3-kinase-dependent translocation of the glucose transporter GLUT1 to the cell surface. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 41. pp. 39337-39348.
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AB - 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.

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