Bentley, Johanne and Itchayanan, Dalina and Barnes, Kay and McIntosh, Elizabeth and Tang, Xiuwen and Downes, C. Peter and Holman, Geoffrey D. and Whetton, Anthony D. and Owen-Lynch, P. Jane and Baldwin, Stephen 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.
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Journal or Publication Title: | Journal of Biological Chemistry |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Departments: | Faculty of Health and Medicine > Biomedical & Life Sciences |
| ID Code: | 9257 |
| Deposited By: | Dr P Jane Owen-Lynch |
| Deposited On: | 03 Jun 2008 09:56 |
| Refereed?: | Yes |
| Published?: | Published |
| Last Modified: | 26 Jul 2012 18:34 |
| Identification Number: | |
| URI: | http://eprints.lancs.ac.uk/id/eprint/9257 |
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