title: Effect of cycloheximide on epidermal growth factor receptor trafficking and signaling.
abstract: Cycloheximide is the most common protein synthesis inhibitor, and is believed to specifically inhibit the cytoplasmic protein synthesis. Here we demonstrate that cycloheximide induces internalization and redistribution of EGF receptor to early endosomes in HeLa cells independent of receptor tyrosine phosphorylation, but dependent on p38 MAPK activity. Degradation of EGF receptor or its downstream effectors was not observed. EGF-induced activation of ERK1/2 was inhibited upon pre-treatment with cycloheximide, but did not activate JNK. The observed effects of treatment with cycloheximide alone are significant and therefore results involving the use of cycloheximide for inhibition of protein synthesis must be interpreted with caution.
authors.affiliation: Dept. of Immunology, Institute for Cancer Research, Oslo University Hospital HF, Montebello, Oslo, Norway. moroks@rr-research.no
authors.forename: Morten P
authors.initials: MP
authors.lastname: Oksvold
authors.forename: Nina Marie
authors.initials: NM
authors.lastname: Pedersen
authors.forename: Lise
authors.initials: L
authors.lastname: Forfang
authors.forename: Erlend B
authors.initials: EB
authors.lastname: Smeland
mesh_terms: D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D003513:Cycloheximide; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases