Akt-dependent transformation: there is more to growth than just surviving

被引:336
作者
Plas, DR
Thompson, CB
机构
[1] Univ Cincinnati, Dept Genome Sci, Genome Res Inst, Cincinnati, OH 45237 USA
[2] Univ Penn, Abramson Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19146 USA
关键词
glycolysis; metabolism; forkhead; FOXO; TSC2; feedback;
D O I
10.1038/sj.onc.1209097
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activation of the Akt/PKB protein kinase family triggers increases in cell size, metabolism and survival. Akt coordinately regulates these fundamental cellular processes through phosphorylation-dependent inactivation of tumor suppressors and activation of trophic signaling. Akt signaling stimulates transport and metabolism of both glucose and amino acids, which in turn support mTOR-dependent increases in protein translation. In addition, Akt activation directs cells to undertake a metabolic conversion from oxidative phosphorylation to aerobic glycolysis. Although this conversion promotes cell growth, it also renders cell survival dependent on a continuous supply of extracellular nutrients, which themselves are required regulatory elements in Akt signal transduction.
引用
收藏
页码:7435 / 7442
页数:8
相关论文
共 96 条
[1]   3-phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase [J].
Alessi, DR ;
Deak, M ;
Casamayor, A ;
Caudwell, FB ;
Morrice, N ;
Norman, DG ;
Gaffney, P ;
Reese, CB ;
MacDougall, CN ;
Harbison, D ;
Ashworth, A ;
Bownes, M .
CURRENT BIOLOGY, 1997, 7 (10) :776-789
[2]   Phosphatidylinositol 3-kinase/Akt signaling is neither required for hypoxic stabilization of HIF-1α nor sufficient for HIF-1-dependent target gene transcription [J].
Arsham, AM ;
Plas, DR ;
Thompson, CB ;
Simon, MC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (17) :15162-15170
[3]   Isoform-specific regulation of insulin-dependent glucose uptake by Akt/protein kinase B [J].
Bae, SS ;
Cho, H ;
Mu, J ;
Birnbaum, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (49) :49530-49536
[4]   STIMULATION OF SUGAR UPTAKE IN CULTURED FIBROBLASTS BY EPIDERMAL GROWTH-FACTOR (EGF) AND EGF-BINDING ARGININE ESTERASE [J].
BARNES, D ;
COLOWICK, SP .
JOURNAL OF CELLULAR PHYSIOLOGY, 1976, 89 (04) :633-639
[5]   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
[6]   Cytokine stimulation of aerobic glycolysis in hematopoietic cells exceeds proliferative demand [J].
Bauer, DE ;
Harris, MH ;
Plas, DR ;
Lum, JJ ;
Hammerman, PS ;
Rathmell, JC ;
Riley, JL ;
Thompson, CB .
FASEB JOURNAL, 2004, 18 (09) :1303-+
[7]  
BAUER DE, IN PRESS ONCOGENE
[8]   The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes [J].
Berwick, DC ;
Hers, I ;
Heesom, KJ ;
Moule, SK ;
Tavaré, JM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (37) :33895-33900
[9]   STIMULATION OF GLYCOLYSIS AND AMINO-ACID UPTAKE IN NRK-49F CELLS BY TRANSFORMING GROWTH FACTOR-BETA AND EPIDERMAL GROWTH-FACTOR [J].
BOERNER, P ;
RESNICK, RJ ;
RACKER, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (05) :1350-1353
[10]   Advances in protein kinase B signalling:: AKTion on multiple fronts [J].
Brazil, DP ;
Yang, ZZ ;
Hemmings, BA .
TRENDS IN BIOCHEMICAL SCIENCES, 2004, 29 (05) :233-242