The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism

被引：2687
作者：
Engelman, Jeffrey A.
Luo, Ji
Cantley, Lewis C. [1 ]
机构：
[1] Harvard Univ, Sch Dent Med, Dept Syst Biol, Boston, MA 02115 USA
[2] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA
[3] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA
来源：
NATURE REVIEWS GENETICS | 2006年 / 7卷 / 08期
关键词：
D O I：
10.1038/nrg1879
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Phosphatidylinositol 3-kinases (PI3Ks) evolved from a single enzyme that regulates vesicle trafficking in unicellular eukaryotes into a family of enzymes that regulate cellular metabolism and growth in multicellular organisms. In this review, we examine how the PI3K pathway has evolved to control these fundamental processes, and how this pathway is in turn regulated by intricate feedback and crosstalk mechanisms. In light of the recent advances in our understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, we discuss the exciting therapeutic opportunities for targeting this pathway to treat these diseases.
引用
收藏
页码：606 / 619
页数：14
相关论文
共 167 条
  • [1] FoxOs at the crossroads of cellular metabolism, differentiation, and transformation
    Accili, D
    Arden, KC
    [J]. CELL, 2004, 117 (04) : 421 - 426
  • [2] The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser307
    Aguirre, V
    Uchida, T
    Yenush, L
    Davis, R
    White, MF
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (12) : 9047 - 9054
  • [3] Phosphoinositide 3-kinase γ:: kinase-dependent and -independent activities in cardiovascular function and disease
    Alloatti, G
    Montrucchio, G
    Lembo, G
    Hirsch, E
    [J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 2004, 32 : 383 - 386
  • [4] The PIK3CA gene is mutated with high frequency in human breast cancers
    Bachman, KE
    Argani, P
    Samuels, Y
    Silliman, N
    Ptak, J
    Szabo, S
    Konishi, H
    Karakas, B
    Blair, BG
    Lin, C
    Peters, BA
    Velculescu, VE
    Park, BH
    [J]. CANCER BIOLOGY & THERAPY, 2004, 3 (08) : 772 - 775
  • [5] Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease
    Backman, SA
    Stambolic, V
    Suzuki, A
    Haight, J
    Elia, A
    Pretorius, J
    Tsao, MS
    Shannon, P
    Bolon, B
    Ivy, GO
    Mak, TW
    [J]. NATURE GENETICS, 2001, 29 (04) : 396 - 403
  • [6] Oncogenic PI3K deregulates transcription and translation
    Bader, AG
    Kang, SY
    Zhao, L
    Vogt, PK
    [J]. NATURE REVIEWS CANCER, 2005, 5 (12) : 921 - 929
  • [7] Increased p85/55/50 expression and decreased phosphotidylinositol 3-kinase activity in insulin-resistant human skeletal muscle
    Bandyopadhyay, GK
    Yu, JG
    Ofrecio, J
    Olefsky, JM
    [J]. DIABETES, 2005, 54 (08) : 2351 - 2359
  • [8] Increased p85α is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess
    Barbour, LA
    Rahman, SM
    Gurevich, I
    Leitner, JW
    Fischer, SJ
    Roper, MD
    Knotts, TA
    Vo, Y
    McCurdy, CE
    Yakar, S
    LeRoith, D
    Kahn, CR
    Cantley, LC
    Friedman, JE
    Draznin, B
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (45) : 37489 - 37494
  • [9] Human placental growth hormone increases expression of the p85 regulatory unit of phosphatidylinositol 3-kinase and triggers severe insulin resistance in skeletal muscle
    Barbour, LA
    Shao, JH
    Qiao, LP
    Leitner, W
    Anderson, M
    Friedman, JE
    Draznin, B
    [J]. ENDOCRINOLOGY, 2004, 145 (03) : 1144 - 1150
  • [10] Candidate gene association study in type 2 diabetes indicates a role for genes involved in β-cell function as well as insulin action
    Barroso, I
    Luan, J
    Middelberg, RPS
    Harding, AH
    Franks, PW
    Jakes, RW
    Clayton, D
    Schafer, AJ
    O'Rahilly, S
    Wareham, NJ
    [J]. PLOS BIOLOGY, 2003, 1 (01) : 41 - 55
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