title: Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis.
abstract: 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.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Lucas
authors.initials: L
authors.lastname: Pelkmans
authors.forename: Eugenio
authors.initials: E
authors.lastname: Fava
authors.forename: Hannes
authors.initials: H
authors.lastname: Grabner
authors.forename: Michael
authors.initials: M
authors.lastname: Hannus
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.forename: Eberhard
authors.initials: E
authors.lastname: Krausz
authors.forename: Marino
authors.initials: M
authors.lastname: Zerial
mesh_terms: D017209:Apoptosis; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D049109:Cell Proliferation; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D013539:Simian virus 40 / Q000502:physiology; D014168:Transferrin / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D022461:Caveolins; D002966:Clathrin; D014168:Transferrin; D011494:Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases