PTEN: The down side of PI 3-kinase signalling

被引:335
作者
Leslie, NR [1 ]
Downes, CP [1 ]
机构
[1] Univ Dundee, Inst Med Sci, Sch Life Sci, Div Cell Signalling, Dundee DD1 5EH, Scotland
基金
英国医学研究理事会;
关键词
phosphoinositide; tumour suppressor; phosphatase; lipid signalling;
D O I
10.1016/S0898-6568(01)00234-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The PTEN tumour suppressor protein is a phosphoinositide 3-phosphatase that, by metabolising phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3), acts in direct antagonism to growth factor stimulated PI 3-kinases. A wealth of data has now illuminated pathways that can be controlled by PTEN through PtdIns(3,4,5)P-3, some of which, when deregulated, give a selective advantage to tumour cells. Early studies of PTEN showed that its activity was able to promote cell cycle arrest and apoptosis and inhibit cell motility, but more recent data have identified other functional consequences of PTEN action, such as effects on the regulation of angiogenesis. The Structure of PTEN includes several features not seen in related protein phosphatases, which adapt the enzyme to act efficiently as a lipid phosphatase. including a C2 domain tightly associated with the phosphatase domain, and a broader and deeper active site pocket. Several pieces of data indicate that PTEN is a principal regulator of the cellular levels of PtdIns(3,4,5)P-3, but work is only just beginning to uncover mechanisms by which the cellular activity of PTEN can be controlled. There also remains the vexing question of whether any of PTEN's cellular functions reflect its evolutionary roots as a member of the protein tyrosine phosphatase superfamily. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:285 / 295
页数:11
相关论文
共 115 条
  • [81] C2-domains, structure and function of a universal Ca2+-binding domain
    Rizo, J
    Südhof, TC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (26) : 15879 - 15882
  • [82] Rohrschneider LR, 2000, GENE DEV, V14, P505
  • [83] Regulation of dauer larva development in Caenorhabditis elegans by daf-18, a homologue of the tumour suppressor PTEN
    Rouault, JP
    Kuwabara, PE
    Sinilnikova, OM
    Duret, L
    Thierry-Mieg, D
    Billaud, M
    [J]. CURRENT BIOLOGY, 1999, 9 (06) : 329 - 332
  • [84] Polarization of chemoattractant receptor signaling during neutrophil chemotaxis
    Servant, G
    Weiner, OD
    Herzmark, P
    Balla, T
    Sedat, JW
    Bourne, HR
    [J]. SCIENCE, 2000, 287 (5455) : 1037 - 1040
  • [85] Receptor tyrosine kinases: Specific outcomes from general signals
    Simon, MA
    [J]. CELL, 2000, 103 (01) : 13 - 15
  • [86] PTEN expression causes feedback upregulation of insulin receptor substrate 2
    Simpson, L
    Li, J
    Liaw, D
    Hennessy, I
    Oliner, J
    Christians, F
    Parsons, R
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (12) : 3947 - 3958
  • [87] PTEN: Life as a tumor suppressor
    Simpson, L
    Parsons, R
    [J]. EXPERIMENTAL CELL RESEARCH, 2001, 264 (01) : 29 - 41
  • [88] Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
    Stambolic, V
    Suzuki, A
    de la Pompa, JL
    Brothers, GM
    Mirtsos, C
    Sasaki, T
    Ruland, J
    Penninger, JM
    Siderovski, DP
    Mak, TW
    [J]. CELL, 1998, 95 (01) : 29 - 39
  • [89] Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers
    Steck, PA
    Pershouse, MA
    Jasser, SA
    Yung, WKA
    Lin, H
    Ligon, AH
    Langford, LA
    Baumgard, ML
    Hattier, T
    Davis, T
    Frye, C
    Hu, R
    Swedlund, B
    Teng, DHF
    Tavtigian, SV
    [J]. NATURE GENETICS, 1997, 15 (04) : 356 - 362
  • [90] Genetic control of cell size
    Stocker, H
    Hafen, E
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 2000, 10 (05) : 529 - 535