title: ERK1/2 regulate exocytosis through direct phosphorylation of the exocyst component Exo70.
abstract: The exocyst is a multiprotein complex essential for exocytosis and plasma membrane remodeling. The assembly of the exocyst complex mediates the tethering of post-Golgi secretory vesicles to the plasma membrane prior to fusion. Elucidating the mechanisms regulating exocyst assembly is important for the understanding of exocytosis. Here we show that the exocyst component Exo70 is a direct substrate of the extracellular signal-regulated kinases 1/2 (ERK1/2). ERK1/2 phosphorylation enhances the binding of Exo70 to other exocyst components and promotes the assembly of the exocyst complex in response to epidermal growth factor (EGF) signaling. We further demonstrate that ERK1/2 regulates exocytosis, because blocking ERK1/2 signaling by a chemical inhibitor or the expression of an Exo70 mutant defective in ERK1/2 phosphorylation inhibited exocytosis. In tumor cells, blocking Exo70 phosphorylation inhibits matrix metalloproteinase secretion and invadopodia formation. ERK1/2 phosphorylation of Exo70 may thus coordinate exocytosis with other cellular events in response to growth factor signaling.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104-6018, USA.
authors.forename: Jinqi
authors.initials: J
authors.lastname: Ren
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D002070:Butadienes; C547754:EXOC7 protein, human; D046912:Multiprotein Complexes; D009570:Nitriles; D011994:Recombinant Proteins; C113580:U 0126; D033921:Vesicular Transport Proteins; D012694:Serine; D004815:Epidermal Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3