Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis

被引:484
作者
Pelkmans, L
Fava, E
Grabner, H
Hannus, M
Habermann, B
Krausz, E
Zerial, M
机构
[1] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany
[2] MPI CBG High Throughput Technol Dev Studio, D-01307 Dresden, Germany
[3] Scionics Comp Innovat GmbH, D-01307 Dresden, Germany
[4] Ceniix Biosci GmbH, D-01307 Dresden, Germany
关键词
D O I
10.1038/nature03571
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Endocytosis is a key cellular process, encompassing different entry routes and endocytic compartments. To what extent endocytosis is subjected to high-order regulation by the cellular signalling machinery remains unclear. Using high-throughput RNA interference and automated image analysis, we explored the function of human kinases in two principal types of endocytosis: clathrin- and caveolae/raft-mediated endocytosis. We monitored this through infection of vesicular stomatitis virus, simian virus 40 and transferrin trafficking, and also through cell proliferation and apoptosis assays. Here we show that a high number of kinases are involved in endocytosis, and that each endocytic route is regulated by a specific kinase subset. Notably, one group of kinases exerted opposite effects on the two endocytic routes, suggesting coordinate regulation. Our analysis demonstrates that signalling functions such as those controlling cell adhesion, growth and proliferation, are built into the machinery of endocytosis to a much higher degree than previously recognized.
引用
收藏
页码:78 / 86
页数:9
相关论文
共 51 条
  • [1] Bound simian virus 40 translocates to caveolin-enriched membrane domains, and its entry is inhibited by drugs that selectively disrupt caveolae
    Anderson, HA
    Chen, YZ
    Norkin, LC
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1996, 7 (11) : 1825 - 1834
  • [2] Systematic genome-wide screens of gene function
    Carpenter, AE
    Sabatini, DM
    [J]. NATURE REVIEWS GENETICS, 2004, 5 (01) : 11 - 22
  • [3] The stress-induced MAP kinase p38 regulates endocytic trafficking via the GDI:Rab5 complex
    Cavalli, V
    Vilbois, F
    Corti, M
    Marcote, MJ
    Tamura, K
    Karin, M
    Arkinstall, S
    Gruenberg, J
    [J]. MOLECULAR CELL, 2001, 7 (02) : 421 - 432
  • [4] Regulated portals of entry into the cell
    Conner, SD
    Schmid, SL
    [J]. NATURE, 2003, 422 (6927) : 37 - 44
  • [5] Clathrin- and caveolin-1-independent endocytosis: entry of simian virus 40 into cells devoid of caveolae
    Damm, EM
    Pelkmans, L
    Kartenbeck, J
    Mezzacasa, A
    Kurzckalia, T
    Helenius, A
    [J]. JOURNAL OF CELL BIOLOGY, 2005, 168 (03) : 477 - 488
  • [6] Signal transduction by the JNK group of MAP kinases
    Davis, RJ
    [J]. CELL, 2000, 103 (02) : 239 - 252
  • [7] Integrins regulate Rac targeting by internalization of membrane domains
    del Pozo, MA
    Alderson, NB
    Kiosses, WB
    Chiang, HH
    Anderson, RGW
    Schwartz, MA
    [J]. SCIENCE, 2004, 303 (5659) : 839 - 842
  • [8] Endocytosis and signaling: An inseparable partnership
    Di Fiore, PP
    De Camilli, P
    [J]. CELL, 2001, 106 (01) : 1 - 4
  • [9] Distinct endocytic pathways regulate TGF-β receptor signalling and turnover
    Di Guglielmo, GM
    Le Roy, C
    Goodfellow, AF
    Wrana, JL
    [J]. NATURE CELL BIOLOGY, 2003, 5 (05) : 410 - 421
  • [10] COMPARTMENTALIZATION OF SHC, GRB2 AND MSOS, AND HYPERPHOSPHORYLATION OF RAF-1 BY EGF BUT NOT INSULIN IN LIVER PARENCHYMA
    DIGUGLIELMO, GM
    BAASS, PC
    OU, WJ
    POSNER, BI
    BERGERON, JJM
    [J]. EMBO JOURNAL, 1994, 13 (18) : 4269 - 4277