title: p38-Mediated phosphorylation of Eps15 endocytic adaptor protein.
abstract: Epidermal growth factor receptor pathway substrate 15 (Eps15) has been suggested to be involved in the endocytosis of cell surface receptors, including epidermal growth factor receptor (EGFR). Eps15 is phosphorylated at Tyr-849 upon stimulation with EGF during endocytic processes. In the present study, we found that stimulation of HeLa cells with EGF or TNF-α induced transient phosphorylation of Eps15 at Ser-796. Inhibition of p38 completely blocked phosphorylation and recombinant p38α directly phosphorylated the residue. These results demonstrate a novel stress kinase-mediated signaling pathway to Eps15 endocytic adapter protein.
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Molecular & Cellular BioAnalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sugiyama
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sakuma
authors.affiliation: Department of Molecular & Cellular BioAnalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishihama
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.affiliation: Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan. Electronic address: hsakurai@pha.u-toyama.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D036103:Nanotechnology; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D053719:Tandem Mass Spectrometry; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C486206:EPS15 protein, human; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D012694:Serine; D004815:Epidermal Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: CME; EGF; EGFR; EGFR pathway substrate 15; Eps15; TAB1; TAK1; TAK1-binding protein 1; TNF-α; UIM; clathrin-mediated endocytosis; epidermal growth factor receptor; p38; transforming growth factor-β-activated kinase 1; tumor necrosis factor-α; ubiquitin-interacting motif