Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking

被引:452
作者
Wiernan, Heather L.
Wofford, Jessica A.
Rathmell, Jeffrey C. [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Dept Immunol, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA
关键词
D O I
10.1091/mbc.E06-07-0593
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cells require growth factors to support glucose metabolism for survival and growth. It is unclear, however, how noninsulin growth factors may regulate glucose uptake and glucose transporters. We show that the hematopoietic growth factor interleukin (IL)3, maintained the glucose transporter Glut1 on the cell surface and promoted Rab11a-dependent recycling of intracellular Glut1. IL3 required phosphatidylinositol-3 kinase activity to regulate Glut1 trafficking, and activated Akt was sufficient to maintain glucose uptake and surface Glut1 in the absence of IL3. To determine how Akt may regulate Glut1, we analyzed the role of Akt activation of mammalian target of rapamycin (mTOR)/regulatory associated protein of mTOR (RAPTOR) and inhibition of glycogen synthase kinase (GSK)3. Although Akt did not require mTOR/RAPTOR to maintain surface Glut1 levels, inhibition of mTOR/RAPTOR by rapamycin greatly diminished glucose uptake, suggesting Akt-stimulated mTOR/RAPTOR may promote Glut1 transporter activity. In contrast, inhibition of GSK3 did not affect Glut1 internalization but nevertheless maintained surface Glut1 levels in IL3-deprived cells, possibly via enhanced recycling of internalized Glut1. In addition, Akt attenuated Glut1 internalization through a GSK3-independent mechanism. These data demonstrate that intracellular trafficking of Glut1 is a regulated component of growth factor-stimulated glucose uptake and that Akt can promote Glut1 activity and recycling as well as prevent Glut1 internalization.
引用
收藏
页码:1437 / 1446
页数:10
相关论文
共 46 条
[1]  
ASANO T, 1991, J BIOL CHEM, V266, P24632
[2]   Chronic myeloid leukaemia: an investigation into the role of Bcr-Abl-induced abnormalities in glucose transport regulation [J].
Barnes, K ;
McIntosh, E ;
Whetton, AD ;
Daley, GQ ;
Bentley, J ;
Baldwin, SA .
ONCOGENE, 2005, 24 (20) :3257-3267
[3]   Regulation of GLUT1 gene transcription by the serine threonine kinase Akt1 [J].
Barthel, A ;
Okino, ST ;
Liao, JF ;
Nakatani, K ;
Li, JP ;
Whitlock, JP ;
Roth, RA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (29) :20281-20286
[4]   Interleukin-3-mediated cell survival signals include phosphatidylinositol 3-kinase-dependent translocation of the glucose transporter GLUT1 to the cell surface [J].
Bentley, J ;
Itchayanan, D ;
Barnes, K ;
McIntosh, E ;
Tang, XW ;
Downes, CP ;
Holman, GD ;
Whetton, AD ;
Owen-Lynch, PJ ;
Baldwin, SA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (41) :39337-39348
[5]   Glucose availability regulates IFN-γ production and p70S6 kinase activation in CD8+ effector T cells [J].
Cham, CM ;
Gajewski, TF .
JOURNAL OF IMMUNOLOGY, 2005, 174 (08) :4670-4677
[6]   Notch promotes survival of pre-T cells at the β-selection checkpoint by regulating cellular metabolism [J].
Ciofani, M ;
Zúñiga-Pflücker, JC .
NATURE IMMUNOLOGY, 2005, 6 (09) :881-888
[7]   Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells [J].
Cong, LN ;
Chen, H ;
Li, YH ;
Zhou, LX ;
McGibbon, MA ;
Taylor, SI ;
Quon, MJ .
MOLECULAR ENDOCRINOLOGY, 1997, 11 (13) :1881-1890
[8]  
Dang CV, 1999, MOL CELL BIOL, V19, P1
[9]   Genetic and metabolic status of NGF-deprived sympathetic neurons saved by an inhibitor of ICE family proteases [J].
Deshmukh, M ;
Vasilakos, J ;
Deckwerth, TL ;
Lampe, PA ;
Johnson, EM .
JOURNAL OF CELL BIOLOGY, 1996, 135 (05) :1341-1354
[10]   Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake [J].
Edinger, AL ;
Thompson, CB .
MOLECULAR BIOLOGY OF THE CELL, 2002, 13 (07) :2276-2288