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
  • [21] REGULATION OF CD4-P56(LCK)-ASSOCIATED PHOSPHATIDYLINOSITOL 3-KINASE (PI 3-KINASE) AND PHOSPHATIDYLINOSITOL 4-KINASE (PI 4-KINASE)
    PRASAD, KVS
    KAPELLER, R
    JANSSEN, O
    DUKECOHAN, JS
    REPKE, H
    CANTLEY, LC
    RUDD, CE
    PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES, 1993, 342 (1299) : 35 - 42
  • [22] PI 3-Kinase p110β Regulation of Platelet Integrin αIIbβ3
    Jackson, Shaun P.
    Schoenwaelder, Simone M.
    PHOSPHOINOSITIDE 3-KINASE IN HEALTH AND DISEASE, VOL 1, 2010, 346 : 203 - 224
  • [23] Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein
    Gout, I
    Middleton, G
    Adu, J
    Ninkina, NN
    Drobot, LB
    Filonenko, V
    Matsuka, G
    Davies, AM
    Waterfield, M
    Buchman, VL
    EMBO JOURNAL, 2000, 19 (15): : 4015 - 4025
  • [24] The phosphoinositide (PI) 3-kinase family
    Foster, FM
    Traer, CJ
    Abraham, SM
    Fry, MJ
    JOURNAL OF CELL SCIENCE, 2003, 116 (15) : 3037 - 3040
  • [25] PI 3-Kinase and Cancer Metabolism
    Cantley, Lewis C.
    CANCER SCIENCE, 2022, 113 : 628 - 628
  • [26] ROLE OF PI 3-KINASE IN MITOGENESIS
    VARTICOVSKI, L
    HARRISONFINDIK, D
    KEELER, ML
    SUSA, M
    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1994, 1226 (01): : 1 - 11
  • [27] Regulation of p110δ PI 3-Kinase Gene Expression
    Kok, Klaartje
    Nock, Gemma E.
    Verrall, Elizabeth A. G.
    Mitchell, Michael P.
    Hommes, Daan W.
    Peppelenbosch, Maikel P.
    Vanhaesebroeck, Bart
    PLOS ONE, 2009, 4 (04):
  • [28] PI 3-KINASE AND CANCER METABOLISM
    Cantley, L. C.
    ANNALS OF ONCOLOGY, 2012, 23 : 21 - 21
  • [29] PI 3-kinase and membrane trafficking
    Emr, SD
    FASEB JOURNAL, 1996, 10 (06): : 1606 - 1606
  • [30] PI 3-kinase and cancer metabolism
    Cantley, Lewis C.
    CANCER RESEARCH, 2016, 76