Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis

被引:602
|
作者
Funamoto, S [1 ]
Meili, R [1 ]
Lee, S [1 ]
Parry, L [1 ]
Firtel, RA [1 ]
机构
[1] Univ Calif San Diego, Ctr Mol Genet, Div Biol, Sect Cell & Dev Biol, La Jolla, CA 92093 USA
关键词
D O I
10.1016/S0092-8674(02)00755-9
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
We have investigated the mechanisms of leading edge formation in chemotaxing Dictyostelium cells. We demonstrate that while phosphatidylinositol 3-kinase (PI3K) transiently translocates to the plasma membrane in response to chemoattractant stimulation and to the leading edge in chemotaxing cells, PTEN, a negative regulator of PI3K pathways, exhibits a reciprocal pattern of localization. By uniformly localizing PI3K along the plasma membrane, we show that chemotaxis pathways are activated along the lateral sides of cells and PI3K can initiate pseudopod formation, providing evidence for a direct instructional role of PI3K in leading edge formation. These findings provide evidence that differential subcellular localization and activation of PI3K and PTEN is required for proper chemotaxis.
引用
收藏
页码:611 / 623
页数:13
相关论文
共 50 条
  • [41] Role of PI 3-kinase in cell signaling
    Cantley, C
    Fruman, D
    Yballe, C
    Rameh, L
    FASEB JOURNAL, 1999, 13 (07): : A1583 - A1583
  • [42] Characterization of a novel PI 3-kinase associated serine kinase distinct from PI 3-kinase.
    Cengel, KA
    Godbout, J
    Nolan, P
    Freund, GG
    DIABETES, 1997, 46 : 1082 - 1082
  • [43] PI 3-Kinase, from the Bench to the Clinic
    Vanhaesebroeck, B.
    JOURNAL OF PATHOLOGY, 2016, 238 : S3 - S3
  • [44] Differential stimulation of PI 3-Kinase by Gβγ
    Kerchner, KR
    Clay, RL
    Watson, N
    Myung, CS
    Garrison, JC
    FASEB JOURNAL, 2004, 18 (05): : A974 - A974
  • [45] Biological roles of PI 3-kinase isoforms
    Vanhaesebroeck, B.
    EJC SUPPLEMENTS, 2007, 5 (04): : 30 - 30
  • [46] PI 3-kinase and cancer: changing accents
    Vogt, Peter K.
    Gymnopoulos, Marco
    Hart, Jonathan R.
    CURRENT OPINION IN GENETICS & DEVELOPMENT, 2009, 19 (01) : 12 - 17
  • [47] TNFα elicits association of PI 3-kinase with the p60TNFR and activation of PI 3-kinase in adherent neutrophils
    Korchak, HM
    Kilpatrick, LE
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 281 (03) : 651 - 656
  • [48] PI 3-kinase mediates leptin activation of KATP channels in rat acutely dispersed hypothalamic
    Mirshamsi, S
    Ashford, MLJ
    JOURNAL OF PHYSIOLOGY-LONDON, 2001, 536 : 18P - 19P
  • [49] A natural ErbB4 isoform that does not activate phosphoinositide 3-kinase mediates proliferation but not survival or chemotaxis
    Kainulainen, V
    Sundvall, M
    Määttä, JA
    Santiestevan, E
    Klagsbrun, M
    Elenius, K
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (12) : 8641 - 8649
  • [50] Lower phosphoinositide 3-kinase (PI 3-kinase) activity and differential expression levels of selective catalytic and regulatory PI 3-kinase subunit isoforms in prefrontal cortex and hippocampus of suicide subjects
    Dwivedi, Yogesh
    Rizavi, Hooriyah S.
    Teppen, Tara
    Zhang, Hui
    Mondal, Amal
    Roberts, Rosalinda C.
    Conley, Robert R.
    Pandey, Ghanshyam N.
    NEUROPSYCHOPHARMACOLOGY, 2008, 33 (10) : 2324 - 2340