New roles for the LKB1→AMPK pathway

被引:215
作者
Hardie, DG [1 ]
机构
[1] Univ Dundee, Wellcome Trust Bioctr, Div Mol Physiol, Dundee DD1 4HN, Scotland
基金
英国惠康基金;
关键词
D O I
10.1016/j.ceb.2005.01.006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The AMP-activated protein kinase(AMPK) is a sensor of cellular energy that is conserved throughout eukaryotes. It is activated by rising AMP, signifying falling energy status caused by starvation for a carbon source or other stress. Binding of AMP to the regulatory gamma subunit triggers phosphorylation of the catalytic a subunit by the upstream kinase LKB1, and the activated kinase switches on ATP-generating catabolic pathways while switching off ATP-requiring processes. AMPK inhibits the TOR (target of rapamycin) pathway by phosphorylating TSC2, thus inhibiting cell growth during times of stress. AMPK is also a target for adipokines that regulate energy balance at the whole-body level.
引用
收藏
页码:167 / 173
页数:7
相关论文
共 53 条
  • [1] AMP-activated protein kinase plays a role in the control of food intake
    Andersson, U
    Filipsson, K
    Abbott, CR
    Woods, A
    Smith, K
    Bloom, SR
    Carling, D
    Small, CJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (13) : 12005 - 12008
  • [2] Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy
    Arad, M
    Moskowitz, IP
    Patel, VV
    Ahmad, F
    Perez-Atayde, AR
    Sawyer, DB
    Walter, M
    Li, GH
    Burgon, PG
    Maguire, CT
    Stapleton, D
    Schmitt, JP
    Guo, XX
    Pizard, A
    Kupershmidt, S
    Roden, DM
    Berul, CI
    Seidman, CE
    Seidman, JG
    [J]. CIRCULATION, 2003, 107 (22) : 2850 - 2856
  • [3] Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy
    Arad, M
    Benson, DW
    Perez-Atayde, AR
    McKenna, WJ
    Sparks, EA
    Kanter, RJ
    McGarry, K
    Seidman, JG
    Seidman, CE
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (03) : 357 - 362
  • [4] Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD
    Baas, AF
    Kuipers, J
    van der Wel, NN
    Batlle, E
    Koerten, HK
    Peters, PJ
    Clevers, HC
    [J]. CELL, 2004, 116 (03) : 457 - 466
  • [5] Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD
    Baas, AF
    Boudeau, J
    Sapkota, GP
    Smit, L
    Medema, R
    Morrice, NA
    Alessi, DR
    Clevers, HC
    [J]. EMBO JOURNAL, 2003, 22 (12) : 3062 - 3072
  • [6] Regulation of fasted blood glucose by resistin
    Banerjee, RR
    Rangwala, SM
    Shapiro, JS
    Rich, AS
    Rhoades, B
    Qi, Y
    Wang, J
    Rajala, MW
    Pocai, A
    Scherer, PE
    Steppan, CM
    Ahima, RS
    Obici, S
    Rossetti, L
    Lazar, MA
    [J]. SCIENCE, 2004, 303 (5661) : 1195 - 1198
  • [8] Genome-wide survey of protein kinases required for cell cycle progression
    Bettencourt-Dias, M
    Giet, R
    Sinka, R
    Mazumdar, A
    Lock, WG
    Balloux, F
    Zafiropoulos, PJ
    Yamaguchi, S
    Winter, S
    Carthew, RW
    Cooper, M
    Jones, D
    Frenz, L
    Glover, DM
    [J]. NATURE, 2004, 432 (7020) : 980 - 987
  • [9] Mutations in the γ2 subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy:: evidence for the central role of energy compromise in disease pathogenesis
    Blair, E
    Redwood, C
    Ashrafian, H
    Oliveira, M
    Broxholme, J
    Kerr, B
    Salmon, A
    Östman-Smith, I
    Watkins, H
    [J]. HUMAN MOLECULAR GENETICS, 2001, 10 (11) : 1215 - 1220
  • [10] AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling.
    Bolster, DR
    Crozier, SJ
    Kimball, SR
    Jefferson, LS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (27) : 23977 - 23980