SEARCH:   Advanced

Blood, 15 February 2008, Vol. 111, No. 4, pp. 2101-2111. Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-06-096297. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-06-096297v1 111/4/2101    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wofford, J. A. Articles by Rathmell, J. C. Search for Related Content PubMed PubMed Citation Articles by Wofford, J. A. Articles by Rathmell, J. C. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival Jessica A. Wofford1, Heather L. Wieman1, Sarah R. Jacobs1, Yuxing Zhao1, and Jeffrey C. Rathmell1,3 1 Department of Pharmacology and Cancer Biology, 2 Department of Immunology, and 3 Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC Lymphocyte homeostasis requires coordination of metabolic processes with cellular energetic and biosynthetic demands but mechanisms that regulate T-cell metabolism are uncertain. We show that interleukin-7 (IL-7) is a key regulator of glucose uptake in T lymphocytes. To determine how IL-7 affects glucose uptake, we analyzed IL-7 signaling mechanisms and regulation of the glucose transporter, Glut1. The IL-7 receptor (IL-7R) stimulated glucose uptake and cell-surface localization of Glut1 in a manner that required IL-7R Y449, which promoted rapid signal transducer and activator of transcription 5 (STAT5) activation and a delayed yet sustained activation of Akt. Each pathway was necessary for IL-7 to promote glucose uptake, as Akt1–/– T cells or PI3-kinase inhibition and RNAi of STAT5 led to defective glucose uptake in response to IL-7. STAT5 and Akt acted in a linear pathway, with STAT5-mediated transcription leading to Akt activation, which was necessary for STAT5 and IL-7 to promote glucose uptake and prevent cell death. Importantly, IL-7 required glucose uptake to promote cell survival. These data demonstrate that IL-7 promotes glucose uptake via a novel signaling mechanism in which STAT5 transcriptional activity promotes Akt activation to regulate Glut1 trafficking and glucose uptake that is critical for IL-7 to prevent T-cell death and maintain homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. E. Johnson, N. Shah, A. A. Bajer, and T. W. LeBien IL-7 Activates the Phosphatidylinositol 3-Kinase/AKT Pathway in Normal Human Thymocytes but Not Normal Human B Cell Precursors J. Immunol., June 15, 2008; 180(12): 8109 - 8117. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020